Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

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.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

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.

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

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.

Mean corpuscular volume ≤100 fl was an independent prognostic factor in patients with myelodysplastic syndrome and bone marrow blast<5 percent / 中华血液学杂志

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Analysis of clinical characteristics, treatment response rate and survival of 77 myelodysplastic syndrome patients with del (5q) syndrome / 中华血液学杂志

Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study / 中华血液学杂志

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia / 中华血液学杂志

Objective: Analysis of the molecular characteristics of eosinophilia. Methods: Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results: Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion: The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.

Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

<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>

Relationship between polymorphisms of tumor necrosis factor alpha gene and primary myelodysplastic syndromes / 中华血液学杂志

<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>

Study on the role of fluorescence in situ hybridization in cytogenetic evaluation of myelodysplastic syndrome / 中华血液学杂志

<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>

Characteristics of cytogenetics and molecular biology in patients with eosinophilia / 中国实验血液学杂志

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.

Study on prognostic significances of different cytogenetic risk categories in patients with primary myelodysplastic syndromes / 中华血液学杂志

<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>

Advance of research on relationship between ABCG2 and drug resistance in hematologic malignancies - review / 中国实验血液学杂志

ABCG2, a half-transporter concerning with the endo and exon-toxin-efflux, plays an important role in protecting the normal tissues from the toxin-hurt as well as mediating the multidrug resistance, because many of the chemotherapeutic drugs are the substrate of ABCG2. In this paper, the advance of research about this gene's single nucleotide polymorphisms (SNPs) was explained concisely. The relationship among ABCG2, the stem cells and the tyrosine kinase inhibitor (TKI) was reviewed. The research about drug resistance related-progress in hematologic malignancies was analyzed retrospectively and the present problems and the perspective in the future were discussed.