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Objective:To explore the characteristics of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients from Northeast China and their impact on prognosis. Methods:The clinical data of 252 CML patients and 49 Ph + ALL patients who were admitted to the First Hospital of Jilin University from January 2013 to October 2018 were retrospectively analyzed. The samples of bone marrow or peripheral blood were collected from patients when imatinib treatment was not effective. Nested polymerase chain reaction (PCR) was used to amplify the BCR-ABL1 kinase domain, and Sequencing Analysis v5.4 software was used to analyze the mutation of BCR-ABL1 kinase domain. Patients were followed up for 6-48 months, and the survival analysis was performed. Results:Among 252 CML patients, the mutations in ABL1 kinase domain were found in 57 patients (22.6%), including 25 patients in the chronic phase, 21 patients in the accelerated phase and 11 patients in the blast crisis; 50 patients had 20 types of single point mutation, and the most common mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the P-loop and C-helix domains; 7 patients had double mutations; patients with multiple mutations had the worst prognosis, with a median overall survival (OS) time of 3.2 months. Among 49 Ph + ALL patients, 17 cases (34.7%) were positive for mutations in the BCR-ABL1 kinase domain, 14 patients had 12 types of single point mutation, and 3 patients had multiple mutations; the median OS time of patients with multiple mutations, mutations located in the P-loop and C-helix domains and mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01). Conclusions:Among the imatinib-resistant CML and Ph + ALL patients from Northeast China, point mutations in the P-loop and C-helix domains are most commonly found. Multiple mutations, mutations in the P-loop and C-helix domains are related to the poor prognosis of the patients.
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Objective@#To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients.@*Methods@#A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform.@*Results@#① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle.@*Conclusions@#1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
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Objective:To determine the derivative chromosome 9 by the method of detecting the ASS gene,and to explore the relationship between the deletion of derivative chromosome 9 and the efficacy and prognosis of the chronic myeloid leukemia (CML)patients. Methods:The materials of 34 CML patients with positive BCR-ABL fusion gene whose ASS genes were detected were retrospectively analyzed. All patients were treated with Extra-signal (ES)probe to detect the derivative chromosome 9.All patients were divided into two groups according to whether they carried the derivative chromosome 9.The blastic phase or the accelerated phase rates in two groups were compared by using Fisher exact probability. Results:All patients were detected by FISH (BCR-ABL ES probe),and all the BCR-ABL fusion signals were positive.6 of 34 patients were found the deletion of ASS gene, among them 1 case blonged to chronic phase,and 5 cases developed into blastic phase or accelerated phase. In the patients without ASS gene deletion,there were 22 cases in chronic phase,and 6 cases in plastic phase or accelerate phase,there was significant difference of blastic phase rate/accelated phase rate between them (P 0.05 ). Conclusion:The CML patients with derivative chromosome 9 (ASS gene deletion)prone to get disease progression, and have a higher proportion in the blastic phase or accelerated phase patients.Derivative chromosome 9 is related to the bad treatment efficacy of TKI and the poor prognosis of CML.
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Objective To investigate the value of 18F-FDG PET-CT in detection and accurate staging of extranodal non-Hodgkin lymphoma (NHL).Methods The results of PET-CT of 94 patients with NHL were retrospectively analyzed.The consistency of checking out lesions and accurate staging by PET-CT were compared with those by other imaging examination in extranodal NHL.Results 432 lesions were checked out by PET-CT, including 319 (73.8 ％) lymphoid tissues and organs with the average SUVmax of 13.4 (3.4-33.4), and 113 (26.2 ％) extranodal lesions with the average SUVmax of 13.5 (3.1-55.0).The detection consistent rate between CT and PET-CT for lymphoid tissues and lymph organ lesions was 95 ％, while the consistent rate of the extranodal lesions was only 54.9 ％.The detection rates of PET-CT for soft tissue, bone and gastrointestinal lesions were higher than those of CT, but the detection rate for the bone marrow lesion was lower than that for the bone marrow cytology.According to the results of PET-CT, the stages of 29 patients (31.0 ％) were re-adjusted, including up-regulated for 75.9 ％ (22/29) because of high detection rates of PET-CT for soft tissue and skeletal lesions, and down-regulated for 24.1％ (7/29) mainly due to the strong resolution capability of PET-CT for detection of non-neoplastic lymph nodes and spleen increasing or effusion.Conclusion 18F-FDG PET-CT can improve the detection rate of NHL extranodal lesions, especially for diffuse non-mass lesions in bone and soft tissues, which facilitates the accurate lymphoma staging.
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Objective To study the mobilizing effect induced by low dose irradiation on mouse peripheral blood(stem/progenitor) cells.Methods Peripheral blood CFU-GM was cultivated in methylcellulose semi-solid culture system,and c-kit~+cells were counted by flow cytometry after low dose irradiation or combined with G-CSF.(Results The) CFU-GM and c-kit~+ cells of peripheral blood in irradiated mice were much higher than those in control mice,the CFU-GM started to increase at 24 h after irradiation,reached maximum at 72 h and stayed high level till 96 h.The CFU-GM and c-kit~+cells at 72 h after 75 mGy irradiation were the most.The CFU-GM and c-kit~+cells in semi-dose G-CSF+75 mGy group were much higher than those in simple low dose irradiation group and were close to those in the group dealed with adequate G-CSF.Conclusion Low dose irradiation can mobilize peripheral blood stem/progenitor cells,and low dose irradiation combined with G-CSF can produce synergetic effect.