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1.
Chinese Journal of Hematology ; (12): 373-379, 2023.
Article in Chinese | WPRIM | ID: wpr-984632

ABSTRACT

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.


Subject(s)
Humans , Aged , Middle Aged , Leukemia, Myelomonocytic, Chronic/genetics , Prognosis , Splicing Factor U2AF/genetics , Mutation , Myelodysplastic Syndromes/genetics , Leukemia, Myeloid, Acute/genetics
2.
Chinese Journal of Hematology ; (12): 276-283, 2023.
Article in Chinese | WPRIM | ID: wpr-984615

ABSTRACT

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.


Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Blast Crisis/drug therapy , Primary Myelofibrosis/genetics , Prognosis , Splenomegaly , Retrospective Studies , Myeloproliferative Disorders/genetics , Mutation , Leukemia, Myeloid, Acute , Janus Kinase 2/genetics
3.
Chinese Journal of Hematology ; (12): 107-114, 2022.
Article in Chinese | WPRIM | ID: wpr-929541

ABSTRACT

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.


Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Bone Marrow/pathology , Exons , Janus Kinase 2/genetics , Mutation , Mutation, Missense , Polycythemia Vera/genetics
4.
Chinese Journal of Hematology ; (12): 48-53, 2022.
Article in Chinese | WPRIM | ID: wpr-929529

ABSTRACT

Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.


Subject(s)
Female , Humans , Pregnancy , Antithrombin III/genetics , Genetic Testing , Mutation , Protein C/genetics , Protein S/genetics , Protein S Deficiency/genetics
5.
Journal of Experimental Hematology ; (6): 52-57, 2018.
Article in Chinese | WPRIM | ID: wpr-278721

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients.</p><p><b>METHODS</b>The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed.</p><p><b>RESULTS</b>Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 10/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048).</p><p><b>CONCLUSION</b>Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 10/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.</p>

6.
Journal of Experimental Hematology ; (6): 617-621, 2017.
Article in Chinese | WPRIM | ID: wpr-271948

ABSTRACT

The spectrum of genetic abnormalities in myelodysplastic syndromes(MDS) has been revealed by high-throughput sequencing. However, the functional role of these mutations in occurrence and development of MDS was not delineated. The mutations in splicing factors have been identified as the commonest gene mutations in MDS. Recently, it was reported that the mutated or dysregulated splicing factors, including SF3B1, SRSF2 and U2AF1, attribute to aberrant mRNA splicing, which leads to hematopoietic dysfunction and drives MDS. These findings will be of great help in searching for candidate therapeutic targets in mis-splicing pathway in MDS. In this review the role of aberrant splicing in pathogenesis of MDS is summarized briefly.

7.
Chinese Journal of Hematology ; (12): 873-876, 2013.
Article in Chinese | WPRIM | ID: wpr-272097

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association of single nucleus polymorphisms(SNP)of tumor necrosis factor alpha (TNF-α) gene (-308 G>A and -238 G>A genotypes) with susceptibility to primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Two SNPs (TNF-α-308 G>A,TNF-α-238 G>A) of TNF-α gene were detected by Taqman probes in 341 MDS patients and 365 unrelated-healthy controls.</p><p><b>RESULTS</b>Compared to healthy controls, the frequency of TNF-α-308 AA+AG genotype and A allele increased (18% vs 10%, P=0.015, 9% vs 5%, P=0.021, respectively) in refractory cytopenia with multilineage dysplasia (RCMD) patients. There was no correlation of TNF-α-308 G>A genotype and allele frequency between MDS and controls. No difference in the genotype and allele frequency of TNF-α-238 G>A were found between controls and MDS or the subtypes of MDS (P>0.05). We did not find any linkage between plasma level of TNF-α and TNF-α-308 G>A or TNF-α-238 G>A genotype. Statistic differences were observed between platelet count[58(1-611)×10⁹/L vs 90(7-352)×10⁹/L]and bone marrow blasts in MDS patients carrying TNF-α-308 G>A GG and AA+AG genotype (P=0.024, 0.019, respectively).</p><p><b>CONCLUSION</b>TNF-α-308 G>A polymorphism was correlated with susceptibility to MDS-RCMD.</p>


Subject(s)
Humans , Case-Control Studies , Gene Frequency , Genetic Predisposition to Disease , Genotype , Myelodysplastic Syndromes , Genetics , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha , Blood , Genetics
8.
Chinese Journal of Hematology ; (12): 205-207, 2013.
Article in Chinese | WPRIM | ID: wpr-235463

ABSTRACT

<p><b>OBJECTIVE</b>To analyze coincidence rate of acute myeloid leukemia (AML) sub-typing between transmission electron microscopy (TEM) and clinical discharge diagnosis.</p><p><b>METHODS</b>Reviewing sub-typing results of TEM, light microscopy, flow cytometric analyzing, molecular biological detection and karyotype in 793 AML cases, comparing their coincidence rates with discharge diagnosis to reveal advantages of AML sub-typing by TEM.</p><p><b>RESULTS</b>General coincidence rates of TEM, light microscopy, flow cytometric analyzing, molecular biological detection and karyotype on AML sub-typing were 63%, 59%, 52%, 47%, 26% and 23% respectively, and clinical coincidence rates of TEM on M1, M2a, M4 and M5, M6, M7, t (8; 21) and t (15; 17) were 39%, 34%, 17%, 74%, 50%, 73%, 87% and 89% respectively.</p><p><b>CONCLUSION</b>TEM has a higher coincidence rate in general AML sub-typing, especially strong screenings on t (15; 17), t (8; 21), M7, M5 and M6, but lower coincidence rates on M1, M2a and M4 sub-typing than other methods.</p>


Subject(s)
Humans , Leukemia, Myeloid, Acute , Classification , Diagnosis , Microscopy, Electron, Transmission , Retrospective Studies
9.
Chinese Journal of Hematology ; (12): 221-224, 2013.
Article in Chinese | WPRIM | ID: wpr-235459

ABSTRACT

<p><b>OBJECTIVE</b>To investigate leukemia transformation rate in myelodysplastic syndrome (MDS) and the relationship with quantitative and type of chromosomal abnormality.</p><p><b>METHODS</b>This study retrospectively analyzed and rediagnosed 138 MDS patients with complete data, investigated the rate and time of leukemia transformation, and analyzed characteristics of chromosome karyotype of de novo patients.</p><p><b>RESULTS</b>29 (21.01%) of 138 patients transformed into leukemia, the rate and the median time of leukemia transformation were 21.01% and 8 (3-24) months, respectively, among which, the rate of leukemia transformation in normal karyotype, abnormal karyotype analysis of ≤5 mitotic cells, and >5 mitotic cells in split phase groups were 6.2%, 23.8% and 38.5%, respectively, and median time of which were 17(13-22), 13(5-23), and 7(3-10) months, respectively. Increased trend of leukemia conversion rate along with increased quantity of chromosomal abnormality was observed (χ²=14.185, P<0.01). Leukemia transformation time negatively correlated with quantity grade of abnormal karyotype (r=-0.631, P<0.01), The leukemia transformation rates in monosomy 7/del 7q, trisomy 8, trisomy 11, complex karyotype and normal karyotype groups were 65.0%, 50.0%, 30.8% and 28.6%, being significantly different (χ²=21.555, P<0.01). Leukemia transformation rate of complex karyotype and monosomy 7/del 7 q was slightly higher than of trisomy 8 and trisomy 11, but both of them were significantly higher than of normal karyotype (χ²=8.054, P=0.005). There were no leukemia transformation cases in del 5q, del 20q, monosomy Y, and trisomy 21 group.</p><p><b>CONCLUSION</b>With or without abnormal chromosome karyotype, quantity and types of abnormal karyotype had important clinical value to predict leukemia transformation in patients with MDS.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Chromosome Aberrations , Karyotyping , Leukemia, Myeloid , Diagnosis , Genetics , Myelodysplastic Syndromes , Genetics , Retrospective Studies
10.
Chinese Journal of Hematology ; (12): 261-265, 2012.
Article in Chinese | WPRIM | ID: wpr-359511

ABSTRACT

<p><b>OBJECTIVE</b>To explore the frequencies of heterozygosity in X-linked G6PD, P55, BTK, and FHL-1 gene exonic polymorphic loci among Chinese females and the value of determination of hematopoietic clonality by detection of these X-chromosome exonic polymorphisms based on X-chromosome inactivation patterns (XCIP)-transcription-based clonality assays (TCA).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood of 446 Chinese healthy females. Allele-specific PCR (ASPCR) or PCR-restriction enzyme digestion method was applied for detecting G6PD, P55, BTK and FHL-1 polymorphisms. Those heterozygotic loci were used as markers to examine the hematopoietic clonality of bone marrow mononuclear cells by TCA from essential thrombocythemia (ET) patients with JAK2V617F mutation and myelodysplastic syndrome (MDS) patients with abnormal karyotype.</p><p><b>RESULTS</b>Among the total 446 genomic DNA samples, the frequencies of heterozygosity in G6PD, P55, BTK and FHL-1 loci were 12.8%, 29.4%, 52.0% and 46.4%, respectively. About 81.4% of females were heterozygous at one or more loci. All 10 ET patients with JAK2V617F mutation and 2 MDS patients with abnormal karyotype, which were heterozygotic in either locus, had monoclonal/oligoclonal hematopoiesis.</p><p><b>CONCLUSION</b>Clonality detection based on X chromosome inactivation patterns-transcription based clonality assays is applicable to about 80% of Chinese females.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Alleles , Asian People , Genetics , Chromosomes, Human, X , Exons , Genes, X-Linked , Genetic Carrier Screening , Genetic Linkage , Glucosephosphate Dehydrogenase , Genetics , Hematopoiesis , Genetics , Polymerase Chain Reaction , Methods , Polymorphism, Single Nucleotide , X Chromosome Inactivation
11.
Chinese Journal of Hematology ; (12): 378-382, 2012.
Article in Chinese | WPRIM | ID: wpr-359479

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical features and prognosis of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients and to improve the cognition of MDS-MF.</p><p><b>METHODS</b>Four hundred and sixty-six primary MDS patients with bone marrow (BM) biopsy were divided into two groups according to whether BM associated with fibrosis, the clinical features and prognosis of the two groups were analyzed retrospectively.</p><p><b>RESULTS</b>167 (35.8%) MDS cases revealed myelofibrosis, of which MF-1 123 cases (26.4%), MF-2 40 cases (8.6%), MF-3 4 cases (0.9%). The proportion of hepatosplenomegaly in MDS-MF group was significantly higher than in MDS without MF group, the difference had statistical significance (P = 0.031). The proliferation of BM biopsy in MDS-MF group was significantly more active than in MDS without MF group. The number of blasts, megakaryocytes and abnormal megakaryocytes in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P < 0.05). Among the 345 patients who had available results of cytogenetic analysis, 121 cases were MDS-MF patients, the proportion of middle and high-risk prognostic group according to IPSS karyotype prognosis groups in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P = 0.047). The median survival was 17 (1 - 60) months in MDS-MF group, and was 32 (1 - 62) months in MDS without MF group. The difference had statistical significance (P = 0.001). Myelofibrosis had independent prognostic significance by multi-variable analysis (P = 0.019).</p><p><b>CONCLUSION</b>The myelofibrosis in MDS is main the proliferation of reticular fiber. The proliferation of reticular fiber is closely related with the number of blast cells, the proliferation and developmental abnormalities of megakaryocytes and the karyotype. The prognosis of MDS-MF patients is poor.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Karyotyping , Myelodysplastic Syndromes , Diagnosis , Pathology , Primary Myelofibrosis , Diagnosis , Pathology , Prognosis , Retrospective Studies
12.
Chinese Journal of Hematology ; (12): 516-521, 2012.
Article in Chinese | WPRIM | ID: wpr-359434

ABSTRACT

<p><b>OBJECTIVE</b>To investigate in vitro characteristics of colony-forming cells (CFC) in patients with myelodysplastic syndrome (MDS) and to compare that in patients with non-severe aplastic anemia (NSAA).</p><p><b>METHODS</b>Data of in vitro CFC and correlation with other related laboratory tests in 155 newly diagnosed MDS patients were analyzed retrospectively, and to compare with data of in vitro CFC in 122 newly diagnosed NSAA patients.</p><p><b>RESULTS</b>Median number of burst-forming units-erythroid (BFU-E) was 9 (0 - 157)/10(5) bone marrow mononuclear cells (BMMNC), colony forming unit-erythroid (CFU-E) 30 (0 - 425)/10(5)BMMNC and colony forming unit-granulocytes/macrophages (CFU-GM) 14 (0 - 125)/10(5)BMMNC in patients with MDS, being significantly lower than those in healthy control; number of BFU-E and/or CFU-E was lower than the lower limit of normal control in 66 cases (42.6%), CFU-GM lower in 3 cases (1.9%) and BFU-E and/or CFU-E with CFU-GM lower in 70 cases (45.2%). Cluster/CFU-GM ratio was significantly lower in low blast group (MDS < 5% blast in bone marrow smear) than that in high blast group (MDS ≥ 5% blast) (0.65 vs 1.0, P = 0.049). In all MDS patients, cluster had positive correlation with each type of CFC (r = 0.415, 0.338, 0.642 for BFU-E, CFU-E, CFU-GM, respectively, P = 0.000), but had negative correlation with neutrophil alkaline phosphatase (N-ALP) positive rate and scores (r(rate) = -0.315, P = 0.001 and r(scores) = -0.257, P = 0.006). The median number of each type of CFC was significantly higher in MDS group than that in NSAA group (BFU-E 9 vs 5/10(5)BMMNC, P = 0.017; CFU-E 30 vs 19.5/10(5)BMMNC, P = 0.023; CFU-GM 14 vs 10/10(5)BMMNC, P = 0.003, respectively). Positive correlation between BFU-E and CFU-E were revealed in both MDS and NSAA group (r(MDS) = 0.712, P = 0.000 and r(NSAA) = 0.757, P = 0.000), with a lower correlation coefficient in MDS (P < 0.05).</p><p><b>CONCLUSIONS</b>Early onset MDS present markedly decreased hematopoietic progenitor cells (HPC), and particularly in erythroid progenitors extensively and severely. The number of BFU-E, CFU-E and CFU-GM can reflect HPC number in vivo but not stand for normal hematopoietic clones, the number of clusters represent pathologic HPC clones but not exactly leukemic blasts.</p>


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Anemia, Aplastic , Pathology , Bone Marrow Cells , Pathology , Cells, Cultured , Granulocyte-Macrophage Progenitor Cells , Cell Biology , Myelodysplastic Syndromes , Pathology , Retrospective Studies , Stem Cells
13.
Chinese Journal of Hematology ; (12): 527-531, 2012.
Article in Chinese | WPRIM | ID: wpr-359432

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical features and survival time in primary myelodysplastic syndromes (MDS) patients accompanied with immunological abnormalities.</p><p><b>METHODS</b>The clinical information, laboratory findings and survival time in 194 untreated primary MDS patients with complete immunological laboratory tests or a past history of autoimmune disease were analyzed retrospectively.</p><p><b>RESULTS</b>There were 37/194 cases (19.07%) with autoimmune abnormalities, including 16/194 (8.25%) with autoimmune disease and 21/194 asymptomatic cases (10.82%) with serologic immunological abnormalities only. There was significant differences in the distribution of age < 60 years old, female, CD4(+)T-cell/CD8(+)T-cell ration < 1 and trisomy 8 (P < 0.05) between the cases with autoimmune disease and without autoimmune abnormalities. The former had a higher 2-year OS, but there was no significance (P = 0.065). There was no significant differences in the distribution of age, MDS-subtype, IPSS risk groups, haemoglobin, absolute neutrophil count, platelets count, the severity of anemia and neutropenia, high level of serologic TNF, chromosomal abnormalities, cytogenetic risk groups and bone marrow cellularity (P > 0.05).</p><p><b>CONCLUSION</b>MDS patients with autoimmune disease are mainly female and younger than 60 years old, with high proportion of trisomy 8 and better prognosis.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Autoimmune Diseases , Myelodysplastic Syndromes , Mortality , Retrospective Studies , Survival Analysis
14.
Chinese Journal of Hematology ; (12): 532-535, 2012.
Article in Chinese | WPRIM | ID: wpr-359431

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the prognostic value of thrombocytopenia in patients with primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Four hundred and nineteen primary MDS patients were retrospectively analyzed. Kaplan-Meier method, Log-rank test and COX regression model were used to evaluate factors that influence the prognosis.</p><p><b>RESULTS</b>Two hundred and fifty-six cases (61.1%) had thrombocytopenia (PLT < 100×10(9)/L), one hundred and three cases (24.6%) had severe thrombocytopenia (PLT < 30×10(9)/L). Overall survival (OS) tended to shorten along with the decreasing of platelet count. Univariate analysis indicated that PL < 30×10(9)/L, MCV ≤ 95 fl, LDH ≥ 300 U/L, lymphocyte-like micromegakaryocyte, nucleated RBC PAS positive, IPSS cytogenetic intermediate- and poor-risk were all related with poor prognosis. Moreover, the prognosis of patients with RCMD, RAEB-Ior RAEB-IIwas poorer than that of the other subgroups. Among these parameters, PLT < 30×10(9)/L, MCV ≤ 95 fl, IPSS cytogenetic intermediate- and poor-risk group and RCMD, RAEB-I and RAEB-II had independent prognostic significance in multivariate analysis. Modified WPSS prognostic model was proposed by adopting PLT, MCV, chromosomal karyotype and WHO classification. The OS of patients with low risk, intermediate-1 risk, intermediate-2 risk and high risk were 59, 28, 14 and 4 months, respectively, and there was a statistically significant difference between the groups (P < 0.05).</p><p><b>CONCLUSION</b>Severe thrombocytopenia indicated unfavorable prognosis, in combination with MCV, chromosomal karyotype and WHO classification, a modified WPSS prognostic model was proposed and worked well for prognostic indication in patients with MDS.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Myelodysplastic Syndromes , Diagnosis , Prognosis , Retrospective Studies , Thrombocytopenia , Diagnosis
15.
Chinese Journal of Hematology ; (12): 839-842, 2012.
Article in Chinese | WPRIM | ID: wpr-323478

ABSTRACT

<p><b>OBJECTIVE</b>To exploit the role of bone marrow (BM) and peripheral blood (PB) fluorescence in situ hybridization (FISH) in cytogenetic evaluation of myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>The metaphase cytogenetics and BM interphase FISH were prospectively compared in 112 cases of de novo MDS. At the same time, comparison of BM and PB FISH was conducted in 56 cases.</p><p><b>RESULTS</b>The differences between metaphase cytogenetics and BM FISH were observed in 22 (54%) of 41 cases with clonal karyotypic abnormalities, most of differences were caused by the limitation of FISH probe panel which could not target all of the regions with aberrations. Only 6 (27%) of 22 differences were involved in our probe regions, the FISH results did not change their cytogenetic risk categories. BM FISH testing was abnormal in 15 (21%) of 71 cases with normal karyotypes, FISH testing was abnormal in 14/51 (27%) and 1/20 (5%) cases with fewer than 20 normal metaphases or more than 20 normal metaphases. Comparison of FISH results of PB and BM samples showed abnormal PB FISH results in 21 (72%) of 29 cases with abnormal BM FISH results, and in 1 (4%) of 27 cases with normal BM FISH results.</p><p><b>CONCLUSION</b>BM FISH should be used to MDS cases with fewer than 20 normal metaphases. Although PB FISH testing is limited by a relatively high false negative rate, it is a reasonable choice to cases with failure of BM aspiration.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , In Situ Hybridization, Fluorescence , Karyotyping , Myelodysplastic Syndromes , Blood , Genetics , Prospective Studies
16.
Journal of Experimental Hematology ; (6): 1216-1220, 2012.
Article in Chinese | WPRIM | ID: wpr-278403

ABSTRACT

The aim of study is to explore the characteristics of cytogenetics and molecular biology in patients with eosinophilia. Bone marrow samples from 79 cases of eosinophilia (AEoC ≥ 1.5×10(9)/L) were detected for PDGFRA/B and FGFR1 gene rearrangement by fluorescence in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR). Forty-four samples were detected for T cell receptor (TCR) clonal rearrangement by PCR. The results showed that among 76 cases the FIP1L1/PDGFRA (F/P) fusion gene was detected in 19 cases, the CHIC2 deletion was detected in 19 cases, the PDGFRA rearrangement was detected in 4 cases, and no FIP1L1 rearrangement was detected. According to the 2008 WHO classification, diagnosis were revised as myeloid neoplasms with PDGFRA/B rearrangement in 20 (42%) of 48 patients and 5 (83%) of 6 patients with hypereosinophilia syndrome (HES) or chronic eosinophilic leukemia (CEL), respectively. The diagnosis in (17%) of 6 patients with CEL was revised as chronic eosinophilic leukemia, not otherwise as specified (CEL-NOS). Clonal cytogenetic abnormalities were detected in 1 case of CEL-NOS and 3 cases with PDGFRB rearrangement. Karyotypic abnormalities involved in chromosome 4q12 were not detected in all of the 21 cases with PDGFRA rearrangement. The clonal TCR gene rearrangement were detected in 33% (5/15), 40% (6/15), and 36% (5/14) cases with PDGFRA/B rearrangement, HES, or secondary eosinophilia, respectively. There was no statistical difference in incidence rate among 3 subgroups. It is concluded that PDGFRA/B rearrangement can be detected in many cases of HES or CEL. Interphase FISH and PCR testing can enhance the diagnostic rate of myeloid neoplasms with PDGFRA/B rearrangement.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Gene Rearrangement , Hypereosinophilic Syndrome , Genetics , In Situ Hybridization, Fluorescence , Karyotyping , Oncogene Proteins, Fusion , Genetics , Receptor, Fibroblast Growth Factor, Type 1 , Genetics , Receptor, Platelet-Derived Growth Factor alpha , Genetics , Receptor, Platelet-Derived Growth Factor beta , Genetics , Reverse Transcriptase Polymerase Chain Reaction , mRNA Cleavage and Polyadenylation Factors , Genetics
17.
Chinese Journal of Hematology ; (12): 705-709, 2012.
Article in Chinese | WPRIM | ID: wpr-278329

ABSTRACT

<p><b>OBJECTIVE</b>To investigate JAK2 exon 12 mutations in patients with Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPN) and the clinical characteristics of patients with JAK2 exon 12 mutants.</p><p><b>METHODS</b>Allele-specific PCR (AS-PCR) was applied to identify JAK2 V617F mutation. Genomic DNA corresponding to exon 12 of JAK2 gene and epigenetic regulator gene (TET2, ASXL1, EZH2) were amplified by polymerase chain reaction (PCR). Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning. SNP genotyping of two 46/1 tag SNPs, rs12340895 and rs10974944, was analyzed using commercially available Taqman assays on the 7500HT real-time PCR instrument according to standard protocols.</p><p><b>RESULTS</b>No JAK2 exon 12 mutation was detected in patients with ET, PMF or JAK2 V617F positive PV. Among 13 JAK2 V617F negative PV patients, JAK2 exon 12 mutation was detected as N542-E543del in 2(15.4%) patients who presented with a phenotype of predominant erythrocytosis and erythroid colonic grown from their bone marrow samples in the absence of exogenous EPO, reduced serum erythropoietin (EPO) level, and no mutations in TET2, ASXL1 or EZH2 genes. One of the affected patients was heterozygous for 46/1 but the second was negative for this haplotype.</p><p><b>CONCLUSION</b>There was no need to detect JAK2 exon 12 mutation in ET, PMF or MPN-U patients without JAK2 V67F mutation. Ph negative MPN patients with JAK2 exon 12 mutations had somewhat unique clinical and laboratory features.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Bone Marrow Neoplasms , Genetics , DNA Mutational Analysis , Exons , Genotype , Janus Kinase 2 , Genetics , Myeloproliferative Disorders , Genetics , Philadelphia Chromosome
18.
Chinese Journal of Hematology ; (12): 819-824, 2011.
Article in Chinese | WPRIM | ID: wpr-345979

ABSTRACT

<p><b>OBJECTIVE</b>To analyze significances of different cytogenetic categories for prognostic stratification in patients with primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Chromosomal abnormalities of 532 primary MDS patients were categorized according to cytogenetic categories of International Prognostic Scoring System (IPSS), Revised IPSS (IPSS-R), and German-Austrian (G-A). Prognostic impacts of different cytogenetic categories and frequent isolated anomalies were investigated.</p><p><b>RESULTS</b>Of 532 patients, 346(65%) patients had clonal cytogenetic abnormalities, including 200(38%) patients had 1 abnormality, 61(11%) patients had 2 abnormalities, and 85(16%) patients had complex abnormalities. Trisomy 8 was the most frequent karyotype abnormality, occurring in 31% of the patients with clonal cytogenetic abnormalities, other frequent anomalies were -7/del(7q)(13%), del(20q)(12%), del(5q)(9%), -18(5%), -21(5%), i(17q)(5%), -Y(4%), -17(4%), +21(4%), -13/del(13q)(4%), and -22(4%). The proportion of poor karyotypes of IPSS was higher in RAEBI and RAEBII among the World Health Organization classifications than in subgroups with less than 5% blasts. The follow-up data were available for 310 patients with a median follow-up duration of 14.5 months. Median survival was 59 months for patients with normal karyotypes and 26 months for those with abnormal karyotypes. According to IPSS cytogenetic categories, the median survivals of good-risk subgroup, intermediate-risk subgroup and poor-risk subgroup were 59, 43 and 12 months, respectively (P < 0.01). For IPSS-R cytogenetic groups, the median survivals of good-risk subgroup, intermediate-risk(int-risk) subgroup, poor-risk and very poor-risk subgroup were 59, 36, 15, and 10 months, respectively (P < 0.01). According to G-A classification, the median survivals of good-risk subgroup, int-1-risk subgroup, int-2-risk subgroup and poor-risk subgroup were 59, 44, 15, and 11 months, respectively (P < 0.01). In frequent isolated karyotypic abnormalities, +8 had a median survival of 44 months, i(17q) had a median survival of 12 months, and -7/del(7q) had a median survival of 14 months.</p><p><b>CONCLUSION</b>In comparison with IPSS and G-A categories, IPSS-R cytogenetic categories are more sophisticated, and can stratify prognosis effectively, but prognostic significances of some karyotypes in IPSS-R still need to be confirmed.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Abnormal Karyotype , Karyotype , Myelodysplastic Syndromes , Classification , Diagnosis , Genetics , Prognosis
19.
Journal of Experimental Hematology ; (6): 81-84, 2011.
Article in Chinese | WPRIM | ID: wpr-244980

ABSTRACT

The aim of study was to investigate the relationship of anemia and neutropenia with ultrastructural abnormalities of erythroblasts and young neutrophils in bone marrow of patients with myelodysplastic syndrome (MDS). Anemia parameters and peripheral neutrophil amount of 74 patients with MDS were measured by automatic hemocyte analyzer. According to Hb value and neutropenia degree, MDS patients were divided into 4 groups: normal, mild, middle and severe anemia or neutropenia. The morbid rate and apoptosis rate of erythroblasts and young neutrophils in bone marrow were measured by transmission electron microscopy (TEM). The results indicated that 68 out of 74 patients were consistent with anemia diagnostic criteria, and 51 out of 68 patients were with neutrocytopenia. TEM showed different abnormal features of erythroblasts and young neutrophils in all patients. The morbid rates of erythroblasts in normal, mild, middle and severe anemia groups were 37 ± 14.7%, 24 ± 9%, 32 ± 16% and 34 ± 21% respectively, while apoptotic rates of erythroblasts in normal, mild, middle and severe anemia groups were 2.25 ± 1.03%, 4.43 ± 2.60%, 8.78 ± 4.04% and 11.67 ± 4.57% respectively. The morbid rate and apoptotic rate of erythroblasts were correlated negatively with Hb and HCT value (p < 0.05). The apoptotic rates of bone marrow young neutrophils in 4 groups with different degree of neutropenia were 6.00 ± 2.67%, 9.50 ± 4.42%, 13.00 ± 3.54% and 17.00 ± 2.39%, which correlated negatively with peripheral neutrophil quantity (p < 0.01). Morbid rates of neutrophils in normal, mild, middle and severe anemia groups were 12.25 ± 16.31%, 13.5 ± 10.01%, 23 ± 8.59% and 51.67 ± 19.67% respectively, which positively correlated with its apoptotic rates (p < 0.01). It is concluded that anemia and neutropenia in patient with MDS are correlated with apoptosis and morbid rate of erythroblasts and young neutrophils in bone marrow, which may result in ineffective hematopoiesis.


Subject(s)
Adult , Female , Humans , Male , Anemia , Pathology , Apoptosis , Bone Marrow Cells , Cell Biology , Myelodysplastic Syndromes , Pathology , Neutropenia , Pathology
20.
Journal of Experimental Hematology ; (6): 239-243, 2011.
Article in Chinese | WPRIM | ID: wpr-244946

ABSTRACT

Classical BCR/ABL fusion gene negative myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), are clonal hematopoietic malignancies sharing in common origin in a multipotential hematopoietic stem cell. The phenotypic variability of the three entities can not be elucidated by JAK2V617F mutation only. Recent discoveries indicated that JAK2V617F allele burden, other mutated genes (such as TET2, ASXL1) and inherited predisposition can play roles in the complicated pathogenesis of MPN, which are summarized in this review.


Subject(s)
Humans , Bone Marrow Neoplasms , Genetics , Genetic Predisposition to Disease , Janus Kinase 2 , Genetics , Mutation , Myeloproliferative Disorders , Genetics , Polycythemia Vera , Genetics , Primary Myelofibrosis , Genetics , Thrombocythemia, Essential , Genetics
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