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Analysis of Myeloid Associated Antigens and JAK1 Gene Mutations in T-ALL

Author: WangWenJuan
Tutor: SunAiNing
School: Suzhou University
Course: Hematological Diseases
Keywords: T cell acute lymphoblastic leukemia myeloid associated antigens gene JAK1 mutation
CLC: R733.7
Type: Master's thesis
Year: 2011
Downloads: 11
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Abstract

【Objective】To study the clinical significance of the presence of myeloid associated antigens in acute T-cell lymphoma leukemia, and evaluate the prevalence of JAK1 gene mutations and their impact on clinical characteristics in this kind of leukemia, while to study whether the jak1 mutations associate with other mutations.【Methods】Newly diagnosed T-ALL patients at the First Affiliated Hospital of Soochow University between February 2006 and March 2011 were collected. DFA and FCM were used to analyze the immunophenotype of 107 patients with T-ALL. The clinical characters and whether to get CR after the first induced chemotherapy including of the overall survival rate were also evaluated. In addition, bone marrow mononuclear cells of 60 newly diagnosed T-ALL patients [44 adult T-ALL patients and 16 pediatric ones] and Jurket,Molt-4,CCRF-CEM cell lines were analyzed. We deceted JAK1 gene mutations by PCR and sequencing. We collected the clinical and lab data of these cases, and then analyzed their clinical characteristics and the relationship between JAK1 gene mutation and NOTCH1, PHF6, FBXW7 gene mutations.【Results】Both T-cell lymphocyte antigens and myeloid associated antigens were co- existing (My+T-ALL) in 70 patients(65.4). 37 patients(34.6%) expressed no myeloid antigens(My-T-ALL).Of all these 70 My+T-ALL, there were 50(46.7%) patients and 34 ones(31.8%) expressing CD13 antigen and CD33 antigen respectively. Co-existing CD13 and CD33 were also 17 patients(15.9%).Only one patient had CD14 antigen and another one had CD15 antigen(0.9% ,respectivly).Follow up 35 patients in all to estimate the clinical factors: there were no significant differences between My+T-ALL group and My-T-ALL group in sex, the peripheral WBC count, weather had other appendant abnormal chromosomal, so did patients with or without CD33, and with or without CD33. The CR rate of the My+T-ALL group and My-T-ALL group on the 28th of the induced chemotherapy are 68.42% and 94.12%(P=0.0964).But the patients who got CD13 antigen(CD13+T-ALL) had a lower CR rate than those whose CD13 were negative(64.71 vs 94.44%,P=0.0408). The CR rate between patients who got CD33 antigen (CD33+T-ALL) and CD33 negative(CD33-T-ALL) were similar(88.89% vs 76.92%, P=0.6478). There was no statistics significance on the two year overall survival.JAK1 mutations were identified in 3 of 44 adult patients(6.8%),two mutations were point mutation, another one is insertion mutation, locating in the exon13,16 and 22, resulting in changes in amino acid sequences. No mutation was found in the childhood T-ALL patients and Jurket, Molt-4,CCRF-CEM cell lines. The molecular genetic markers most frequently associated with JAK1 mutation were PHF6 mutation (P=0.0032)【Conclusions】My+T-ALL is a common kind of T-ALL, CD13+T-ALL has a lower CR rate after one course of induced treatment, but the 2 years OS rates were not different. The JAK1 mutations were found in about 5% newly-diagnosed T cell acute lymphoblastic leukemia, which was lower than those reports abroad. JAK1 gene mutations were particularly prevalent in T-ALL cases harboring mutations of PHF6.

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