RUNX1 ABERRATIONS IN ETV6/RUNX1-POSITIVE AND ETV6/RUNX1-NEGATIVE PATIENTS: Its Hemato-Pathological and Prognostic Significance in a Large Cohort (619 Cases) of ALL

Abstract

A large-cohort study (619) of acute lymphoblastic leukemia (ALL) revealed an ETV6/RUNX1 (previously known as TEL/AML1) incidence of 18% in pediatric B-cell precussor ALL, indicating no geographical heterogeinity. Association of CD34-negative phenotype, peak incidence in the 3- to 7-year age group, and a comparatively low frequency of ETV6 homologue loss in ETV6/RUNX1-positive cases were distinct findings in this series. Additional genetic changes, such as ETV6 loss, extra RUNX1, ETV6/RUNX1 duplication, and MLL aberrations in the ETV6/RUNX1-positive group, supported the hypothesis of the ETV6/RUNX1 leukemogenic model that these secondary changes are necessary for leukemogenesis rather than progression of disease. This study disclosed RUNX1 alterations in the ETV6/RUNX1-negative group of BCP-ALL that encourages the investigation of RUNX1 at a large scale with longer follow-up, which will focus on the prognostic importance and the underlying biology of disease.

Cytogenetic Profile in 7209 Indian Patients with <i>de novo</i> Acute Leukemia: A Single Centre Study from India

“…This finding is consistent with our previous study [27] and another cohort of 928 patients [Nahar A et al in communication]. Data from various studies from Asian countries also indicated low prevalence (13% -19%) of ETV6/RUNX1 [54]- [56].…”

“…The peak incidence of ETV6/RUNX1 was in lower age group of 1 -10 years as reported in our previous studies as well as in studies from other Asian countries [27] [52] [55] [59]. Trisomy 21 and ETV6 allelic loss were most frequent additional abnormalities in ETV6/RUNX1 positive group, however these abnormalities were common in overall BCP-ALL patients [27] [59].…”

“…Fluorescence in situ hybridization (FISH) and conventional cytogenetics are the main strategies for cytogenetic workup of acute leukemia in disease management [13] [25]- [27]. Independent FISH analysis is used in several laboratories due to high sensitivity for detection of various cryptic structural and submicroscopic abnormalities, and also copy number changes in AL within short turnaround time [25]- [30].…”

Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea

“…Several studies have reported deletion of the non-translocated ETV6 allele as a recurrent abnormality occurring in conjunction with ETV6/RUNX1 [6-9]. In our cohort, del(12p) was found in 14 patients (22%), but was not found to affect EFS.…”

Characterization of cryptic rearrangements, deletion, complex variants of PML, RARA in acute promyelocytic leukemia

“…[1617] We have also detected nonreciprocal BCR-ABL with 9q deletion/res ABL deletion/res BCR deletion in a large CML series of 2000 cases (our unpublished data). Our vast experience in various hematological malignancies like Acute Lymphoblastic Leukemia (ALL)[18–20] in lymphoma[21] which support the notion that genomic deletions followed by translocations are common events in hematological malignancies.…”