Molecular cytogenetics and clinical features analysis of children with acute lymphoblastic leukemia: a single-center study / 中华实用儿科临床杂志

ABSTRACT

Objective:To analyze the relationship between molecular cytogenetic abnormalities and clinical characteristics of acute lymphoblastic leukemia (ALL) in childhood .Methods:A total of 403 patients newly diagnosed with ALL in the Department of Hematology, Shanghai Children′s Hospital from January 2009 to December 2018 were enrolled in this study.All the patients had completed the test of bone marrow smear cytology, immunotyping, karyotype analysis, and fluorescence in situ hybridization (FISH).Results:(1)There were 240 males (59.6%) and 163 females (40.4%) aged (5.31±3.46)years.There were 374 patients(92.8%) with B cell acute lymphoblastic leukemia (B-ALL)and 29 patients(7.2%) with T cell acute lymphoblastic leukemia (T-ALL). (2)Cytogenetics A total of 311 cases (77.2%) showed mitosis in the chromosomal karyotype analysis, of which 126 cases were abnormal (abnormality detection rate was 40.5%), including 15.4% (48/311cases) hyperdiploid.(3)Fusion gene Positive fusion genes were found in 110 cases (27.3%), including TEL/AML1 gene in 70 cases (17.4%), BCR/ ABL in 13 cases (3.2%), MLL in 19 cases (4.7%). From 2015-2018, 8 cases (4.0%) of PBX1/TCF3 fusion gene, 1 case of EBF1-PDGFRB fusion gene, 6 cases of SIL/TAL1 fusion gene were detected, SIL/TAL1 positive patients which were accounting for 33.3% of T-ALL improved the detection rate of T-ALL molecular abnormalities.Patients with positive BCR/ ABL were older than those with positive TEL/AML1 and positive MLL[(8.01±3.11) years vs.(3.89±1.84) years, (1.56±1.25) years, P<0.001]; patients with positive PBX1/TCF3 [6.58±4.83) years]were older than those with positive TEL/AML1 and positive MLL (all P<0.05); patients with positive MLL were younger than those with positive TEL/AML1 [(1.56±1.25) years vs.(3.89±1.84) years, P=0.001]; the white blood cell (WBC) count of positive MLL patients was higher than that of positive TEL/AML1 and positive BCR/ ABL patients [(76.97±19.87)×10 9/L vs.(16.94±2.28)×10 9/L, P=0.002; (76.97±19.87)×10 9/L vs.(20.53±6.49)×10 9/L, P<0.05]; the WBC count of PBX1/TCF3 positive children was higher than that of positive TEL/AML1 patients [(85.75±30.32)×10 9/L vs.(16.94±2.28)×10 9/L, P=0.002]. The immunotyping of positive MLL patients was dominated by early precursor B-ALL (14/19 cases), while the immunotyping of TEL/AML1 and BCR/ABL positive patients were dominated by common-B-ALL(57/70 cases and 11/15 cases). (4)The detection rates of chromosome karyotype analysis, FISH, and polymerase chain reaction (PCR) were used to detect molecular genetic abnormalities in primary ALL patients, the detection rate was 40.5% (126/403 cases), 69.2% (279/403 cases), and 29.7% (60/202 cases), respectively.The difference was statistically significant ( P<0.001). There was no significant difference in the abnormality detection rate between chromosome karyotype analysis and PCR ( P=0.71). (5)There was no significant difference in the detection rate of molecular cytogenetic abnormalities between different genders and age groups ( P=0.651, 0.721). There was a significant difference between the WBC count ≥50 × 10 9/L group and <50 × 10 9/L group(37/51 cases vs.107/352 cases, P<0.001). The detection rate of B-ALL genetic abnormalities was higher than that of T-ALL genetic abnormalities(275/374 cases vs.14/29 cases, P=0.005). Conclusions:There are a higher proportion of hyperdiploidy chromosomes in children ALL.The distribution of fusion genes is related to age, primary white blood cell count, and immunotyping.The three detection methods complement each other and greatly improve the detection rate of genetic abnormalities.The detection rate of T-ALL genetic abnormality is low, and new detection methods may be needed.