1.Low WT1 transcript levels atdiagnosis predicted poor outcomes ofacute myeloid leukemia patients witht(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation
YaZhenQin ; YuWang ; HongHuZhu ; RobertPeterGale ; MeiJieZhang ; QianJiang ; HaoJiang ; LanPingXu ; HuanChen ; XiaoHuiZhang ; YanRongLiu ; YueYunLai ; BinJiang ; KaiYanLiu ; Huang XIAOJUN
Chinese Journal of Cancer 2016;35(7):350-358
Background:Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy. This study aimed to evaluate the impact of Wilm tumor gene?1 (WT1) transcript levels and cellular homolog of the viral oncogenev?KIT receptor tyrosine kinase (C?KIT) mutations at diagnosis, andRUNX1?RUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.
Methods:Eighty?eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation (allo?HSCT) were included. Patients who achieved remission, received two or more cycles of consolidation chemotherapy, and had a positive measureable residual disease (MRD) test result (deifned as<3?log reduction inRUNX1?RUNX1T1 transcript levels compared to baseline) after 2–8 cycles of consolidation chemotherapy were recommended to receive allo?HSCT. Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels andC?KIT mutations at diagnosis, andRUNX1?RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.
Results:Patients who had aC?KIT mutation had signiifcantly lowerWT1 transcript levels than patients who did not have aC?KIT mutation (6.7%±10.6% vs. 19.5%±19.9%,P<0.001). LowWT1 transcript levels (≤5.0%) but notC?KIT mutation at diagnosis, a positive MRD test result after the second cycle of consolidation chemotherapy, and receiv?ing only chemotherapy were independently associated with high cumulative incidence of relapse in all patients (hazard ratio [HR]=3.53, 2.30, and 11.49; 95% conifdence interval [CI] 1.64–7.62, 1.82–7.56, and 4.43–29.82;P=0.002, 0.034, and<0.001, respectively); these conditions were also independently associated with low leukemia?free survival (HR=3.71, 2.33, and 5.85; 95% CI 1.82–7.56, 1.17–4.64, and 2.75–12.44;P<0.001, 0.016, and<0.001, respectively) and overall survival (HR=3.50, 2.32, and 4.34; 95% CI 1.56–7.82, 1.09–4.97, and 1.98–9.53;P=0.002, 0.030, and<0.001, respectively) in all patients.
Conclusions: Testing forWT1 transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission. A randomized study is warranted to determine whether allo?HSCT can improve prog?nosis in these patients.
2.Leukemia-associated immunophenotypes in 415 childhood and adult patients with B lineage acute lymphoblastic leukemia by multiparametric flow cytometry analysis.
Yan-Rong LIU ; Shan-Shan CHEN ; Yan CHANG ; Jia-Yu FU ; Le-Ping ZHANG ; Hui WANG ; Ling-Di LI ; Hong-Hu ZHU ; Gui-Lan LIU ; Dao-Pei LU ; Xiao-Jun HUANG
Journal of Experimental Hematology 2006;14(5):853-857
To evaluate the significance of FCM in minimal residual disease (MRD) detection, the immunophenotyping and leukemia-associated immunophenotypes (LAIP) of leukemia cells from 273 adult and 142 childhood patients with B lineage acute lymphoblastic leukemia (B-ALL) were detected by four to six antibody combinations of 4-color CD45/SSC gating multiparametric flow cytometry (FCM). The results showed that the B-ALL patients could be classified into 4 subtypes based on different expression CD34 and CD10: subtype I (CD34(+)/CD10(-)), subtype II (CD34(+)/CD10(+)), subtype III (CD34(-)/CD10(+)), subtype IV (CD34(-)/CD10(-)). The LAIP was observed in 100% and 92% patients of subtype I and subtype II, respectively, whereas only 79.2% in subtype III. The incidence of LAIP in total B-ALL cases was 90% by using the antibodies detected in this investigation. There was no significantce different for incidence of LAIP between adult and pediatric patients. LAIP was observed in 77.6% of patients by labeling only CD34/CD10/CD19/CD45 4-color antibody combination. It is concluded that in 90% of childhood and adult B-ALL patients LAIP can be found, which suits MRD detection by multiparameter flow cytometry.
Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antigens, CD34
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analysis
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B-Lymphocytes
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immunology
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Burkitt Lymphoma
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classification
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immunology
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pathology
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Cell Lineage
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Female
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Flow Cytometry
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methods
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Humans
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Immunophenotyping
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Male
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Middle Aged
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Neoplasm, Residual
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diagnosis
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Neprilysin
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analysis
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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classification
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immunology
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pathology