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Objective@#To evaluate the clinical characteristics of T-cell acute leukemia/lymphoma (T-ALL) and explore the prognosis significance of early T-cell precursor leukemia/lymphoma.@*Methods@#A cohort of 126 patients diagnosed with T-ALL from 2008 to 2014 in West China Hospital, Sichuan University were enrolled in this study. They were further categorized by immunophenotype according to the expression of T-cell lineage markers CD1a, CD8, CD5 and one or more stem cell or myeloid markers. The laboratory indicators and prognosis factors were also statistically analyzed.@*Results@#Of all patients, the ratio of male to female was 2.5∶1, with the median age of 25 years old (range 14 to 77) . The percentage of ETP-ALL was up to 47.6%. T-ALL patients showed higher ratio in first clinical remission rate (CR1) than T-LBL ones (64.4% vs 30.8%, P=0.032) . Group with WBC count higher than 50×109/L at presentation showed higher ration of achieving CR1 than those lower than 50×109/L (78.4% vs 50.9%, P=0.010) . In comparison with the non-ETP-ALL, ETP-ALL patients had older age of onset (P<0.001) , lower WBC count (P<0.001) , lower risk of CNS involvement (10.0% vs 30.2%, P=0.009) and slightly inferior overall survival (P=0.073) . T-cell lineage markers CD1a-, CD8- and CD4- positive patients had higher CR1 than their corresponding negative ones (P=0.002, P=0.000, P=0.001) , while CD33- and CD56- positive patients had lower ratio of achieving CR1 than their negative ones, respectively (P=0.035, P=0.035) .@*Conclusion@#Flow cytometry and associated markers for immunophenotyping was of significance in the diagnosis and prognosis monitoring of T-ALL/LBL. The percentage of ETP-ALL/LBL subtype was high in Chinese adolescent and adult T-ALL patients. ETP-ALL/LBL was a high risk subtype, which needs more precise standard for diagnosis and advanced therapies for better outcome.
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Objective To detect the expression of Hedgehog signaling pathway receptor Smoothened (Smo) protein in chronic myeloid leukemia (CML) CD34-positive (CD34+) cells, and to explore the role of Hedgehog signaling pathway in CML stem/progenitor cells. Methods Seventeen chronic phase (CP) and 6 advanced phase (AP) CML patients who were diagnosed in West China Hospital of Sichuan University from September 2010 to March 2011 and 10 People (healthy people and patients without hematologic malignances) as control were included in this study. The expression levels of Smo protein were detected by the protocol of indirect immunofluorescence labeling for cytometry and analyzed statistically. Results The mean of relative fluorescence intensity of Smo protein was 282.5±102.4, 188.8±55.4 and 354.0±297.9 in the CML-CP, CML-AD and control groups, respectively. The difference between CML-CP and CML-AD groups was statistically significant (P= 0.032). However, there were no significant differences between the CML-CP, CML-AD groups and control group (both P>0.05). The percentage of CD34+Smo+cells was (58.9±24.2)％, (42.6±17.6)％and (55.9±29.7) ％ in the CML-CP, CML-AD and control groups, respectively. There were still no significant differences between the CML-CP, CML-AD groups and control group (F= 0.950, P= 0.398). The mean of relative fluorescence intensity of Smo protein in the CML-CP patients with tyrosine kinase inhibitor (TKI) (9 cases) administered and without TKI (8 cases) were 282.3 ±122.6 and 282.6 ±82.4, respectively. There were no significant differences between the two groups(P=0.157). Conclusions Flow cytometry can qualitatively and quantitatively detect the expression level of Smo protein in CML CD34+cells. Smo expression is associated with stage of CML;TKI could not inhibit the activation of the Hedgehog signaling pathway in CML CD34+cells.
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Objective@#To review the clinical characteristics of a pedigree with inherited hemorrhagic disease to explore its molecular pathogenesis.@*Methods@#The clinical data of the pedigree with inherited hemorrhagic disease were collected. After extracting DNA, next generation sequencing was utilized to detect the potential gene mutation. The changes of RASGRP2 transcript of this proband and his parents were detected using RT-PCR to compare with normal control.@*Results@#The phenotype of the proband in this pedigree with inherited platelet dysfunction and bleeding disorder was similar to variant Glanzmann’s thrombasthenia, the maximum aggregations of platelet in response to the physiological agonists including ADP, epinephrine and arachidonic acid were significantly lower, leading to severe spontaneous mucosal bleeding. Integrin αIIbβ3 gene mutation was not detected, but another gene mutation RASGRP2 IVS3-1 stood out. The mutation was homozygous in the proband and heterozygosis in both of his parents. Two transcript types were detected in the proband, without transcripts coding functional RASGRP2 protein, however, his parents had functional transcripts and abnormal transcripts, with the normal transcripts in the majority.@*Conclusions@#The RASGRP2 IVS3-1 gene mutation was responsible for the inherited hemorrhagic disease. The RASGRP2 IVS3-1 gene mutation led to abnormal alternative splicing, without formation of functional RASGRP2 protein. The RASGRP2 protein is at the nexus of calcium-dependent platelet activation and hemostasis after damage of blood vessels. Spontaneous mucosal bleeding was a result of the lack of the functional RASGRP2 protein. This was the first report of RASGRP2 gene mutation resulting in bleeding disorder in China, and also the first report of the mutation type of RASGRP2 IVS3-1.
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Objective To evaluate the relationship between plasma imatinib and its effect in the treatment of chronic myeloid leukemia(CML). Methods Fifty-one CML patients were included in this study,who began taking imatinib from July 2005 to February 2008, with 34 cases of male, and 17 cases of female.Nine patients took imatinib at dose of 300 mg/d, 37 patients took imatinib at dose of 400 mg/d, and 5 patients took imatinib at dose of 600 mg/d. High-performance liquid chromatography was used to test imatinib plasma levels. Results The imatinib plasma levels was imatinib dose-related, and the imatinib plasma trough levels significantly varied between individuals[(342-4688)ng/ml]. The imatinib plasma levels was significant lower in 300 mg/d dose group [(1037±514) ng/ml] than 400 mg/d dose group [(2123±1016) ng/ml] (t =2.34, P =0.032),and the effective rate was 66.7 % (6/9) in 300 mg/d dose group, which was lower than 400 mg/d dose group of 89.19 % (33/37) (χ2=7.14, P =0.008). In 300 mg/d and 400 mg/d dose groups, 39 patients achieved effective treatment, and their imatinib plasma levels was significant higher than that of 7 patients who did not achieved effective treatment (t =2.25, P =0.037). The ROC curve results suggested that clinical treatment may be poor when the imatinib plasma level was lower than 1050 ng/ml (sensitivity was 84.6 %, specificity was 71.1 %).Conclusion The imatinib plasma levels was dose-related, and significantly varied between individuals.Clinical treatment effect may be poor when the imatinib plasma level was lower than 1050 ng/ml.
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Objective Comparative evaluation of flow cytometric immunophenotyping in the diagnosis and differentiation of lymphadenopathy,lymphoma and reactive lymphoid hyperplasia. Methods Ninty-nine fine-needle aspiration specimens from patients with tentative clinical lymphoprofierative disorders were consecutively analyzed by both cytology and flow cytometry with histology results as the gold standard. The three color antibodies including CD3,CD3,CD4,CD5,CD10,CD19,CD20,CD23,CD45,K,λ,FMC7 and CD34 were used for cell composition evaluation and cells with abnormal phenotype. Lymphoma cases were classified according to new WHO classification and subtypes were categorized by immunophenotypic analysis. The results from flow cytometry and cytology were compared. Results By cytological study, 40 of 99 cases were diagnosed with lymphoma, 29 cases were diagnosed with metastatic carcinoma, and 30 cases were diagnosed with reactive lymphoid hyperplasia, necrosis or tuberculosis. Among them, 2 non-Hodgkin lymphoma(NHL) cases were misdiagnosed as reactive lymphoid hyperplasia by cytology. Biopsy was performed in 18 cases of NHL including 16 B-NHL and 2 T-NHL By flow cytometry study, 35 of 99 eases were diagnosed with lymphoma, including 4 cases of lymphoblast lymphoma, 1 case of T-cell lymphoma, and 30 eases of other B-NHL For those 30 cases of B-NHL, 28 cases showed monoclonal light chain expression, and k: λ orλ: k atios exceed 3: 1, and B-cell proportion was (73. 2±27. 2)%. Twenty-six cases could be sub-classified by immunophenotyped. Among 16 histologically confirmed B-NHL cases, only 2 cases diagnosed with follicular lymphoma showed discrepancy with flow cytometry results. In all cases diagnosed with reactive lymphoid hyperplasia and metastasis carcinoma , no abnormal lymphocytes can be found, and k: λ or k: λ ratios were less than 3: 1. Conclusions Fine-needle aspiration analysis with flow eytometrie immunophenotyping can be helpful in diagnosis and differential diagnosis as well as sub-classification of NHL