Clinical significance of PDGFRβ gene testing in hematological tumors / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and laboratory characteristics of hematological tumors with different types of abnormalities in platelet derived growth factor β (PDGFRβ) gene.@*METHODS@#A retrospective analysis was carried out on 141 patients with abnormal long arm of chromosome 5 (5q) and comprehensive medical history data from Changhai Hospital Affiliated to Naval Medical University from 2009 to 2020, and their clinical data were collected. R-banding technique was used for chromosomal karyotyping analysis for the patient's bone marrow, and fluorescence in situ hybridization (FISH) was used to detect the PDGFRβ gene. The results of detection were divided into the amplification group, deletion group, and translocation group based on FISH signals. The three sets of data column crosstabs were statistically analyzed, and if the sample size was n >= 40 and the expected frequency T for each cell was >= 5, a Pearson test was used to compare the three groups of data. If N < 40 and any of the expected frequency T for each cell was < 5, a Fisher's exact test is used. Should there be a difference in the comparison results between the three sets of data, a Bonferroni method was further used to compare the data.@*RESULTS@#In total 98 patients were detected to have PDGFRβ gene abnormalities with the PDGFRβ probe, which yielded a detection rate of 69.50% (98/141). Among these, 38 cases (38.78%) had PDGFRβ gene amplifications, 57 cases (58.16%) had deletions, and 3 (3.06%) had translocations. Among the 98 cases, 93 were found to have complex karyotypes, including 37 cases from the amplification group (97.37%, 37/38), 55 cases from the deletion group (96.49%, 55/57), and 1 case from the translocation group (33.33%, 1/3). Analysis of three sets of clinical data showed no significant gender preponderance in the groups (P > 0.05). The PDGFRβ deletion group was mainly associated with myeloid tumors, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (P < 0.001). The PDGFRβ amplification group was more common in lymphoid tumors, such as multiple myeloma (MM) (P < 0.001). The PDGFRβ translocation group was also more common in myelodysplastic/myeloproliferative tumors (MDS/MPN).@*CONCLUSION@#Tumors with PDGFRβ gene rearrangement may exhibit excessive proliferation of myeloproliferative tumors (MPN) and pathological hematopoietic changes in the MDS, and have typical clinical and hematological characteristics. As a relatively rare type of hematological tumor, in addition to previously described myeloid tumors such as MPN or MDS/MPN, it may also cover lymphoid/plasma cell tumors such as multiple myeloma and non-Hodgkin's lymphoma.

Clinical features analysis of B-cell acute lymphoblastic leukemia with KMT2A::AFF1 gene expression / 中华检验医学杂志

Objective:To analyze the correlation between clinical features and prognosis or prognostic risk factors in patients with KMT2A::AFF1 gene positive B-ALL.Methods:Retrospective cohort study was conducted. 167 cases of B-ALL admitted to the Shanghai General Hospital and the Naval Medical University Affiliated First Hospital from April 1, 2011 to July 31, 2022 were divided into groups according to gene types. 22 cases with KMT2A::AFF1 positive B-ALL were enrolled as the experimental group, 54 cases with BCR::ABL gene positive B-ALL as control group 1 and 91 cases with KMT2A::AFF1 and BCR::ABL gene negative B-All as control group 2. The median age of first diagnosis in the experimental group, control group 1 and control group 2 were 43.5(30.5, 56), 43.5(34, 55) and 32(24, 46) respectively. The median white blood cell counts of the three groups were 142.4(25.7, 247.2)×10 9/L, 37.6(15.7, 102.2)×10 9/L and 13.4(4.3, 33.0)×10 9/L, respectively. Allo-HSCT rates in three groups were 45.5%, 72.2% and 72.5% respectively. Using SPSS 26.0 software, the statistical methods of nonparametric rank sum test, chi-square test, Kaplan-Meier and Cox regression were used to analyze and compare the differences in clinical characteristics, chemotherapy and prognosis between the experimental group and the control groups, and to analyze the risk factors and the differences in prognosis of allo-HSCT in the experimental group. Results:The age difference between the experimental group and the control group 2 was significant ( Z=-2.151, P=0.031). The white blood cell count in experimental group was significantly higher than that in control group 1 ( Z=-2.363, P=0.018) and control group 2 ( Z=-4.886, P<0.001). The rate of allo-HSCT in experimental group was lower than that in control group 1(45.5% vs 72.2%, χ 2=4.890, P=0.027) and control group 2 (45.5% vs 72.5%, χ 2=5.897, P=0.015). The remission rates of the patients in three groups after receiving one course of chemotherapy were 60%(12/20), 83.3%(45/54) and 76.6%(69/90); the remission rates after two courses of chemotherapy were 25%(5/20), 7.4%(4/54) and 12.2% (11/90), and the non-remission rates of more than two courses of treatment were 15%(3/20), 9.3%(5/54) and 11.1%(10/90), respectively. The effect of chemotherapy in experimental group was worse than that in control group 1 ( Z=-1.979, P=0.048). There was no significant difference between the three groups in sex, whether the chromosome is a standard-risk karyotype, hemoglobin at the time of initial onset, platelet count and percentage of bone marrow blast cells. The overall survival rate (OS) of experimental group was significantly lower than that of control group 1 and control group 2(23.9% vs 36.7%, χ 2=7.608, P=0.006 and 23.9% vs. 44.8%, χ 2=6.442, P=0.011), and the 3-year recurrence-free survival (RFS) was also lower than that of the other two groups (14.0% vs 57.6%, χ 2=17.823, P<0.001 and 14.0% vs 48.2%, χ 2=16.432, P<0.001). There was a significant difference in the total OS rate between the experimental group and the group without allo-HSCT (45.0% vs 9.2%, χ 2=15.254, P<0.001). Univariate analysis showed that age was the risk factor of RFS in the experimental group, and allo-HSCT therapy was the protective factor of OS. Multivariate analysis showed that allo-HSCT was an independent protective factor for OS in the experimental group. Conclusions:Patients with KMT2A::AFF1 positive B-ALL had higher white blood cells, less sensitivity to chemotherapy and poor prognosis. Age was a risk factor of RFS in KMT2A::AFF1 positive B-ALL, and allo-HSCT could improve the prognosis.

Acute promyelocytic leukemia with NPM鄄RARα fusion gene positive: report of one case and review of literature / 白血病·淋巴瘤

Objective To investigate the diagnosis, treatment and prognosis of acute promyelocytic leukemia (APL) with NPM_RARα fusion gene positive. Methods One APL patient with NPM_RARα fusion gene positive who was diagnosed by using morphology, immunology, cytogenetics, molecular biology and multiplex fluorescence in situ hybridization in Changhai Hospital in November 2014 was retrospectively analyzed, and the patient was induced with retinoic acid and treated with DA (daunorubicin + cytarabine) regimen, followed by 4 courses of cytarabine consolidation therapy. Results Abnormal promyelocyte accounted for 0.64 by morphology. And the group of cells expressed myeloperoxidase (MPO), CD13, CD15, CD117, and CD7, CD11c, CD79a, CD123 weakly expressed or not by immunophenotype analysis; karyotype analysis showed 45, XY, t(5;17), 7p-,-16[8]/46, idem,+20[5]/45, idem,-8,+20[2]/46, XY[5]; the fusion gene screening showed that the expression level of NPM_RARα was 416.98% compared with that of APL; molecular complete remission was obtained after the consolidation therapy, but the patient relapsed after 34 months. Finally, the patient died of abnormal coagulation and respiratory failure, with overall survival of 35 months. Conclusion APL with NPM_RARα fusion gene positive is a rare type of acute leukemia, and the main treatment method is retinoic acid combined with myeloid chemotherapy regimen, which has a favorable efficacy but a poor prognosis.

Myeloid neoplasms with eosinophilia and abnormal PDGFRA/B: report of three cases and review of literature / 白血病·淋巴瘤

Objective To investigate clinical and hematological features of myeloid neoplasms with eosinophilia and abnormal PDGFRA/B and the effect of imatinib. Methods The data of three eosinophilia patients with abnormal PDGFRA/B fusion gene in Changhai Hospital, the Second Military Medical University and 22 Chinese cases reported in Chinese medical journals were analyzed. Thirty-one cases of idiopathic hypereosinophilic syndrome from Changhai Hospital, the Second Military Medical University were used as the controls. Results Compared with idiopathic hypereosinophilic syndrome, no differences were found in age, percentage of bone marrow eosinophils and counts of platelets in peripheral blood in myeloid neoplasms with eosinophilia and abnormal PDGFRA/B (all P ＞0.05), but statistical differences were found in gender (χ2＝5.080, P ＝ 0.016), peripheral blood white blood cell count (t ＝ 4.908, P ＝ 0.001), eosinophilic granulocyte absolute value (χ2＝ 17.230, P ＝ 0.001) and hemoglobin concentration (t ＝ 2.770, P ＝ 0.013). The median follow-up time was 17 months (3-108 months) in 24 myeloid neoplasms patients with eosinophilia and abnormal PDGFRA/B from Chinese report. Complete hematopoietic remission (CHR) rate was 91.7 % (22/24) after the treatment of imatinib. The total complete molecular remission (CMR) rate was 75.0 % (18/24). The median time of remission was 3 months (1-8 months). CMR in patients with PDGFRA and with PDGFRB was 76.5 % (13/17) and 85.7 % (6/7), respectively. Only one patient (4.2 %) died of disease relapse. Conclusion Imatinib has a favorable effect on myeloid neoplasms with eosinophilia and abnormal PDGFRA/B featured by distinct hematologic and clinical manifestations.

Secondary macrophage activation syndrome in rheumatoid arthritis: a case report with literature review / 中华风湿病学杂志

Objective To investigate the clinical characteristics of Macrophage activation syndrome (MAS) in patients with rheumatoid arthritis (RA), so as to reduce misdiagnosis. The objective of this paper was to improve the comprehensive and systematic understanding of rheumatoid arthritis complicated with macrophage activation syndrome. Methods The clinical data of one patient with macrophage activation syndrome secondary to RA were analyzed retrospectively, and the related literatures were reviewed. Results The patient was a 65 year old male with ahistory of RA for 14 years. The patient presented with symmetrical multi-joint pain aggravated with stiffness for 14 years and was admitted because of aggravation for 2 weeks. He failed many drugs for the treatment of rheumatoid arthritis was ineffective accompanied with intermittent leukocytopenia. After bone marrow aspiration and biopsy, the phenomenon of phagocytosis of macrophages was clearly diagnosed. He was treatment with high dose corticosteroid +CsA+ human immunoglobulin and his condition wasimproved. Literature was searched in PubMed, Wan Fang medical network database, RA+MAS. Finally, 12 related articles was yielded, and a total of 14 patients, including 8 males, 6 females. Four patients were adults and 10 were children. The shortest duration was 0.5 months, the longest was 24 months. Fever, skin rash, arthritis, enlargement of the liver or spleen, decreased of blood cells count, elevation of liver transaminase, increase of triglyceride, and a series of symptoms and laboratory parameters were observed in the course of the disease. Conclusion When rheumatoid arthritis patients show decreased blood leukocytes and can not be explained by other causes, the differential diagnosis should be carefully performed to rule out secondary macrophage activation syndrome. Always be awake of the risks and dangers of rheumatoid arthritis complicated with macrophage activation syndrome. Early diagnosis and timely are important to improve prognosis.

Secondary macrophage activation syndrome in rheumatoid arthritis: a case report with literature review / 中华风湿病学杂志

Objective To investigate the clinical characteristics of Macrophage activation syndrome (MAS) in patients with rheumatoid arthritis (RA), so as to reduce misdiagnosis. The objective of this paper was to improve the comprehensive and systematic understanding of rheumatoid arthritis complicated with macrophage activation syndrome. Methods The clinical data of one patient with macrophage activation syndrome secondary to RA were analyzed retrospectively, and the related literatures were reviewed. Results The patient was a 65 year old male with ahistory of RA for 14 years. The patient presented with symmetrical multi-joint pain aggravated with stiffness for 14 years and was admitted because of aggravation for 2 weeks. He failed many drugs for the treatment of rheumatoid arthritis was ineffective accompanied with intermittent leukocytopenia. After bone marrow aspiration and biopsy, the phenomenon of phagocytosis of macrophages was clearly diagnosed. He was treatment with high dose corticosteroid +CsA+ human immunoglobulin and his condition wasimproved. Literature was searched in PubMed, Wan Fang medical network database, RA+MAS. Finally, 12 related articles was yielded, and a total of 14 patients, including 8 males, 6 females. Four patients were adults and 10 were children. The shortest duration was 0.5 months, the longest was 24 months. Fever, skin rash, arthritis, enlargement of the liver or spleen, decreased of blood cells count, elevation of liver transaminase, increase of triglyceride, and a series of symptoms and laboratory parameters were observed in the course of the disease. Conclusion When rheumatoid arthritis patients show decreased blood leukocytes and can not be explained by other causes, the differential diagnosis should be carefully performed to rule out secondary macrophage activation syndrome. Always be awake of the risks and dangers of rheumatoid arthritis complicated with macrophage activation syndrome. Early diagnosis and timely are important to improve prognosis.

Effect of quality control cycle on reducing the false negative rate of minimal residual disease of flow cytometry in patients with acute myeloid leukemia / 白血病·淋巴瘤

Objective To analyze the application of quality control cycle (QCC) in reducing the false negative rate of minimal residual disease (MRD) of flow cytometry in patients with acute myeloid leukemia (AML). Methods In AML patients with abnormal fusion gene detected in hematology laboratory of Changhai Hospital during the year of 2014, the prevalence of AML-MRD detected both by flow cytometry (FCM) and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) were analyzed retrospectively. The possible causes of false negative rate of flow cytometric MRD referring to PCR were further deeply analyzed, and the improvement measures were adapted from January 2015 to December 2015 and further judged all according to the QCC methods. Results Pareto diagram showed that the dilution and coagulation of the specimen, the improper analysis strategy and the incomplete combination of the MRD index [composition ratio:83.3 % (60/72)] were the main factors leading to the leakage of FCM MRD in 2014. The QCC group devised measures to reduce the dilution probability of bone marrow and develop a standard operating procedures (SOP) for sampling and testing, strengthen the maintenance of the flow instrument and more importantly, focused on optimizing the antibody panels and gated strategies referring to the current two main kinds of MRD detection combination modes on the basis of the latest advances published in 2015. Finally, the undetected rate of AML-MRD was reduced by FCM from 14.8 % (72/486) in 2014 to 2.6 % (16/620) in 2015. Conclusions The QCC can effectively reduce the leakage rate of flow cytometric AML MRD, improve the ability of laboratory quality control and the ability to solve problems. Solving problems with QCC is thus worthy of being popularized.

Acute promyelocytic leukaemia with translocations of t(15;17)(q22;q21) and rob(13;21): a case report and literatures review / 中华血液学杂志

<p><b>OBJECTIVE</b>To report an acute promyelocytic leukaemia (APL) case with translocation of rob (13;21) t(15;17) (q22;q21) and review its clinical and laboratory characteristics.</p><p><b>METHODS</b>Based on routine karyotype analysis and bone marrow morphology, we further used double color double fluorescent in situ hybridization (DCDF-FISH) and reverse transcriptase PCR (RT-PCR) to examine the patient's abnormities on cytogenetic and molecular biology, and reveal the clinical characteristics of this rare translocation also from the related literatures.</p><p><b>RESULTS</b>The clinical manifestation and bone marrow morphology examination of this patient were in accordance with pathologic feature of APL. On first visit, immunophenotyping analysis showed positive myeloid markers. Through R-banding, the patient's karyotype was confirmed as 45, XX, rob(13;21) t(15;17) (q22;q21) [6]/45, XX, rob(13;21) [14]. FISH results showed that 68.9% cells were typical t(15;17) pattern. The positive rates of fusion gene of PML-RARα detected by RT-PCR was 25.8%. Patient was treated by induction and consolidation therapy, the karyotype was 45, XX, rob(13;21 )[20] after complete remission. The positive rate of fusion gene of PML-RARα by FISH and its level were 2.5% and 0.003% respectively.</p><p><b>CONCLUSION</b>APL with rob (13;21) t(15;17) (q22;q21) was very rare, which was accorded with clinical and laboratory characteristics of APL. The value of chromosome abnormality as a prognostic marker in APL needs to be further observed..</p>

Acute lymphoblastic leukemia with atypical bcr-abl rearrangement: a case report and literature review / 白血病·淋巴瘤

Objective To investigate the detection methods of atypical bcr-abl rearrangement with b3a3 fusion transcript,and to describe the characteristics of this fusion gene.Methods Karyotype analysis,FISH and RT-PCR were applied to detect the break point of bcr-abl fusion gene in a patient who was diagnosed as acute lymphoblastic leukemia.Results The karyotype of the patient was expressed as 45,XY,-7,t(9;22)(q34;q1 1).The translocation event in chromosome 9 and 22 could be successfully detected by FISH,and a rare bcr-abl rearrangement with b3a3 fusion transcript was detected by RT-PCR with specific primers.Conclusions The rare e14a3 (b3a3) fusion of bcr-abl gene is present in this patient.Clinical laboratories using commercial kits that do not cover such rare fusions are likely to generate false result,thereby declaring combination of various methods to detect fusion genes is necessary.More studies are needed to explore the function and significance of rare bcr-abl fusion genes.