Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL

Genes

Natalya Risinskaya¹  Tatiana Obukhova¹  Sergey Kulikov¹  Ksenija Zarubina¹  Olga Gavrilina¹  Elena Parovichnikova¹  Anna Yushkova¹  Hunan Julhakyan¹  Julia Chabaeva¹  Ekaterina Kotova¹  Andrey Sudarikov¹  Galina Isinova¹  Yana Kozhevnikova² 

[1] National Research Center for Hematology, Novy Zykovski Lane, 4a, 125167 Moscow, Russia;School of Medicine, Lomonosov Moscow State University, 27-1, Lomonosovsky Prospect, 119991 Moscow, Russia;

关键词: short tandem repeat (STR);    acute lymphoblastic leukemia;    loss of heterozygosity (LOH);    uniparental disomy (UPD);    chromosomal microarray (CMA);   

DOI  :  10.3390/genes13030398

来源: DOAJ

【 摘 要 】

Despite the introduction of new technologies in molecular diagnostics, one should not underestimate the traditional routine methods for studying tumor DNA. Here we present the evidence that short tandem repeat (STR) profiling of tumor DNA relative to DNA from healthy cells might identify chromosomal aberrations affecting therapy outcome. Tumor STR profiles of 87 adult patients with de novo Ph-negative ALL (40 B-ALL, 43 T-ALL, 4 mixed phenotype acute leukemia (MPAL)) treated according to the “RALL-2016” regimen were analyzed. DNA of tumor cells was isolated from patient bone marrow samples taken at diagnosis. Control DNA samples were taken from the buccal swab or the blood of patients in complete remission. Overall survival (OS) analysis was used to assess the independent impact of the LOH as a risk factor. Of the 87 patients, 21 were found with LOH in various STR loci (24%). For B-ALL patients, LOH (except 12p LOH) was an independent risk factor (OS hazard ratio 3.89, log-rank p-value 0.0395). In contrast, for T-ALL patients, the OS hazard ratio was 0.59 (log-rank p-value 0.62). LOH in particular STR loci measured at the onset of the disease could be used as a prognostic factor for poor outcome in B-ALL, but not in T-ALL.

【 授权许可】

Unknown