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.
1766 The MPD are characterized by clonal neoplastic proliferation of one or more of the myeloid lineage in the bone marrow. The BCR/ABL fusion gene is a key genetic marker for CML an the mutation JAK2 V617F is present by over 95% of patients with PV and more than 50% of patients with ET and IMF. Both JAK2 V617F and BCR/ABL result in perturbation of tyrosine kinases and their downstream signaling pathway. The coexistence of BCR/ABL fusion gene and JAK2 V617F mutation have been described in some cases. In the differential diagnosis of MPD vs CML we performed both determinations BCR/ABL fusion gene and JAK2 V617F mutation and observed high frequency of the coexistence. Material and Methods: We performed 350 JAK2V617F and 1500 BCR-ABL PCR assays in LAOH, between January 2011 and July 2012, for the patients with suspected MPD vs CML that were sent from diferents hospitals. This cases without definitive diagnosis were maked both test and the cohort was of 142 patients. Peripheral blood or bone marrow samples were included of 56 cases with CML, 48 cases of isolated thrombocytosis, 34 cases in which total blood count disclosed elevation of ≥2 myeloid cell types and 4 cases with PV diagnosis. RNA and DNA were extracted using Trizol® reagent and Quiagen® commercial kit, the RT-PCR from b3a2/b2a2 BCR-ABL transcript was performed according to protocols standarized. For JAK2 V617F we using the allele-specific PCR method and the restiction enzyme method with BsaXI enzyme wich restriction site is present in exon 14 of JAK2. To validate the specificity of our result we sequenced the PCR products in 10 cases and two normal controls. Results. Of the 142 patients evaluated for both JAK2 V617F and BCR-ABL fusion gene, 18 patients were positive for both (12.7%). Ten with CML de novo, seven cases with ET, and one case in follow-up with imatinib. The average age of these JAK2 V617F mutation and BCR-ABL positive patients (n=18) was 63.5 (ranging from 45–82) and in patients JAK2 V617F mutation and BCR-ABL negative (n=124) were 58 years old (rank 18–85). The patient with CML in therapy with imatinib by one year, was present increase WBC; and his molecular analysis for JAK2 V617F was positive and also BCR/ABL+. The patient′s treatment regimen was modified, with initiation of hydroxyurea and imatinib; the patient achieved complete hematological response. Discussion. The others cases reports in the literature are most often a JAK2 V617F+ MPN developed in the setting of a previously diagnosed CML undergoing treatment with a tyrosine kinase inhibitor, or alternately, CML developed months to years after patients had been diagnosed with a JAK2 V617F+ MPN. In this report the most of our cases the BCR-ABL and JAK2 V617F positive cells were detected before the treatment. This studies have suggested two possibilities to account for expression of BCR-ABL and JAK2 V617F anomalies concomitant in a single patient. The first is that there are two clones each having BCR-ABL and JAK2 V617F mutation and another possibility is a single clone concurrently possesses both BCR-ABL and JAK2 V617F. It remains to be seen whether or not this patients would benefit from combined treatment with tyrosine kinase inhibitor and interferon or hydroxyurea. The clinical following up of this patients help us to response this questions. We have the highest frequency of concurrent JAK2 V617F mutation and BCR-ABL fusion gene reported, but is neccessary determined the true incidence in a greater number of patients with CML and MPD. Disclosures: No relevant conflicts of interest to declare.
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