Frequency of p190 and p210 BCR-ABL Fusions Genes in Acute Lymphoblastic Leukemia in a Long Group of Adults and Childhood

Abstract

The Ph chromosome is a translocation (9;22)(q34;q11), that results in the constitutive activation of the BCR/ABL tyrosine kinase. The incidence of BCR/ABL in Acute Lymphoblastic Leukemia (ALL) increases with age, from less than 5% in younger children to 20-30% in older adults, with a peak incidence in patients aged 35-50 years. BCR/ABL1 has diverse breakpoints, in adult patients with Ph+ ALL the p190BCR/ABL transcript e1a2/e3a2 may be documented in 50-70%; p210BCR/ABL b2a2/b3a2 in 15-30% of patients and <1% having both breakpoint. Childhood patients with Ph+ ALL fusion genes present p190BCR/ABL transcipt e1a2/e3a2 in 90% and the remaining present other fusion transcrit or co-expression of both p190 and p210 BCR-ABL. OBJETIVE. The aim of this study was identify the occurrence of fusion genes to p190 and p210 BCR-ABL rearrangements in adult and childhood patients with ALL. METHODS. We include between 2008-2015 870 patients with ALL de novo from seven different hospitals from México, the 45% (394) were childood and the rest 55% (476) were adults. All patients were studied to RT-PCR multiplex and nested in RNA for fusion transcripts 190 and p210 BCR-ABL, at diagnosis, according to the international BIOMED-1 protocol. RESULTS. From 870 patients with ALL, the most frequent subtype FAB were L2 (87%) and second L1 (13%). The immunophenotype by B-ALL was to 80%, bilineal in 5% and the rest have not data. The overall incidence to BCR-ABL in both children and adults with ALL were to 17% [147/870]. The analysis by age group were; in 476 adults with ALL, their average age was 37 years old (range 17-84 years) and their incidence of BCR-ABL positive was 20% (95/476 cases). The distributions by type of fusion transcript were 83% p190 and 17% p210; we did not observe co-expression of transcripts to BCR-ABL. In children patients the average age was 9 years old (range 0.1-16 years), the incidence of BCR-ABL was 13.2% (52/394 cases). The distributions by type of fusion transcript to BCR-ABL were p190 78.8%; p210 13.4% and their co-expression by both isoforms 8%. CONCLUSION. The 20% frequency for BCR-ABL1 in adults with ALL is concordant with others reports published, with values from 17% to 37% with predominancy of p190 (83%). In our pediatric patients group with ALL, document a frequency of 13.2% by BCR-ABL1 positive; it is higher than other populations reporting 5-10%. The distributions of fusion transcript p190 and p210 coincides with previous prevalence estimates in other countries where p190 transcript was the most frequent. But the coexpression of both isoforms [p190/p210] were 8% it has not been reported in this age group with ALL. In conclusion, we recommend to identify the BCR-ABL transcript type in every patients with ALL at diagnosis, using a RT-PCR verified method for P190/p210 and followed the patient by mesure the impact clinical and will be adjust the treatment like o plus the cytogenetic studies. Disclosures No relevant conflicts of interest to declare.

Cytogenetic and Fluorescence in situ Hybridization Profile of Pediatric Acute Lymphoblastic Leukemia in a University Hospital in South India

“…The frequency of the BCR/ABL1 positive cases at 4.8% (n = 4) was similar to that observed in other populations reporting 5-10% [20], highlighting the fact that analysis of this fusion transcript should be mandatory in all cases of ALL as these patients may benefit from the addition of tyrosine kinase inhibitors. The frequency of ETV6/ RUNX1 at 8.3% (n = 7) was higher than that observed in 2 studies from India reporting a frequency of 4.3%-7.3% [21,22].…”

In Utero Development and Immunosurveillance of B Cell Acute Lymphoblastic Leukemia

“…BCP-ALL with t(9;22)(q34;q11), also referred to as Ph + ALL, is present in ≈2% of pediatric ALL, but is significantly more common in adults [ 22 , 55 ]. The majority of pediatric patients with BCR-ABL1 fusion genes harbor the p190 BCR-ABL1 subtype [ 56 ]. This chromosomal translocation leads to the formation of the BCR-ABL1 oncogene, encoding for a tyrosine kinase.…”

Dasatinib in the Management of Pediatric Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

“…This is because it comes from different breakpoints on chromosome 22 in the BCR gene and encodes for three principal isoforms of aberrant protein kinases (namely, p190, p210, and p230) with distinct molecular mass (20). The frequency pattern of distribution of these isoforms is slightly different from CML to ALL and between adulthood and childhood (21,22). In about 90% of cases of childhood Ph+ ALL, t(9;22) mostly occurs in the minor breakpoint cluster region and produces a constitutional activate tyrosin kinase protein (of 190 kDa, p190 BCR-ABL1).…”

“…In about 90% of cases of childhood Ph+ALL, t(9;22) mostly occurs in the minor breakpoint cluster region and produces a constitutional activate tyrosin kinase protein (of 190 kDa, p190 BCR-ABL1 ). The remaining cases are mainly represented by p210 isoforms ( 22 ).…”