Target-specific next-generation sequencing technology was used to analyze 112 genes in adult patients with acute lymphoblastic leukemia (ALL). This sequencing mainly focused on the specific mutational hotspots. Among the 121 patients, 93 patients were B-ALL (76.9%), and 28 patients (23.1%) were T-ALL. Of the 121 patients, 110 (90.9%) harbored at least one mutation. The five most frequently mutated genes in T-ALL are NOTCH1, JAK3, FBXW7, FAT1, and NRAS. In B-ALL, FAT1, SF1, CRLF2, TET2, and PTPN1 have higher incidence of mutations. Gene mutations are different between Ph+ALL and Ph−ALL patients. B-ALL patients with PTPN11 mutation and T-ALL patients with NOTCH1 and/or FBXW7 mutations showed better survival. But B-ALL with JAK1/JAK2 mutations showed worse survival. The results suggest that gene mutations exist in adult ALL patients universally, they are related with prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0431-1) contains supplementary material, which is available to authorized users.

Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in Ph+B-ALL patients. IKZF1 gene deletion is the most common gene deletion in adult B-ALL, followed by CDKN2A/B deletion. In Ph-B-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with IKZF1 or CDKN2A/B deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with IKZF1 deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of Ph-B-ALL patients with double deletion of IKZF1and CDKN2A/B may be much worse than that of patients with IKZF1 or CDKN2A/B alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive Ph-B-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult Ph-B-ALL patients.

Abstract. The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), ETS variant 6 (ETV6), RB transcriptional corepressor 1 (RB1), BTG anti-proliferation factor 1 (BTG1), early B-cell factor 1 (EBF1), cyclin dependent kinase inhibitor 2A/2B (CDKN2A/2B) and cytokine receptor like factor 2 (CRLF2) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed. Gene deletions were detected in 58/87 (66.7%) ALL patients. The most common deletions were observed in the following genes: IKZF1 (40.6%), CDKN2A (31.9%), CDKN2B (29%), PAX5 (21.7%), RB1 (14.5%) and BTG1 (10.1%). B cell-ALL (B-ALL) patients with CDKN2A/2B deletions exhibited poor 2-year overall survival (OS; P=0.055) and relapse-free survival (RFS; P=0.054) rates. CDKN2A/2B deletions were associated with poor 2-year OS (P=0.045) and RFS (P= 0.071) rates in Philadelphia chromosome positive (Ph