Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries

Abstract

It has been generally acknowledged that the diagnosis, treatment and prognosis evaluation of leukemia largely rely on an adequate identification of genetic abnormalities. A systemic analysis of genetic aberrations was performed in a cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL) in China. The pediatric patients had higher incidence of hyperdiploidy and t(12;21) (p13;q22)/ETV6 --RUNX1 than adults (Po0.0001); in contrast, the occurrence of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all Po0.0001). In B-ALL, the existence of Ik6 and that of BCR --ABL were statistically correlated (Po0.0001). In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR --ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6 --RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients. The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20 --38%) or adult patients (2.36% vs 6.77 --12%) in our study than in Western reports. In addition, the frequencies of HOX11L2 in adult patients were much higher in our cohort than in Western countries (20.69% vs 4 --11%). In general, it seems that Chinese ALL patients bear more adverse prognostic factors than their Western counterparts do.

Clinical characteristics of acute lymphoblastic leukemia in male and female patients: A retrospective analysis of 705 patients

“…The present finding of the gender ratio indicated a male predominance, which is consistent with previous studies of Chinese ALL patients (3,4,(8)(9)(10)(11)(17)(18)(19)(20)(21). As shown in Table II, the gender ratio of ALL patients from various areas of China ranged between 1.37 (20) and 1.92 (3), indicating that regional differences exerted a minor influence on the gender predominance.…”

“…The majority of previous studies on Chinese patients conveyed limited data regarding gender difference (4,(8)(9)(10)(11). In addition, the patients in these studies were from Northern China, such as Beijing (12), Eastern China, such as Shanghai (5,6,(9)(10)(11), and central China, such as Wuhan (10).…”

Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases

“…Results of our large-scale screening for molecular markers have shown that the distributions of molecular markers in 10 --14-year and 15 --19-year age groups were similar, although the latter group seemed to have more chromosomal structural changes and less numeric changes (Chen et al 15 ). However, their outcomes differed from each other dramatically in prognostic analysis: the survival of 10 --14-year age group was closer to that of the 1 --9-year age group, with a median OS not been reached, whereas the survival of the 15 --19-year age group was closer to that of adults (X20 years), with a median OS of 26 months (95% CI 12.6 --39.4).…”

Fighting against hematological malignancy in China: from unique system to global impact

“…Using exome sequencing, the mutations of DNA-methyltransferase 3A (DNMT3A) in acute monocytic leukemia were found to be correlated with the alterations of DNA methylation patterns and gene expression profiles. In cohorts of thousands of patients with newly diagnosed ALL, it was revealed that Chinese ALL patients demonstrated more adverse prognostic factors, such as breakpoint cluster region-Abelson (BCR-ABL), than western patients [38,39]. In AML, DNMT3A and mixed-lineage leukemia (MLL) mutations were associated with OS and DFS, whereas biallelic CCAAT/enhancer-binding protein alpha (CEBPA) or nucleophosmin1 (NPM1) mutations without DNMT3A mutations exhibited a better OS.…”