Analysis of the clinico-hematological relevance of the breakpoint location within M- BCR in chronic myeloid leukemia

Bennour, Ayda; Ouahchi, Ines; Achour, Bechir; Zaier, Monia; Youssef, Yosra; Khelif, Abderrahim; Saad, Ali; Sennana, Halima
March 2013
Medical Oncology;Mar2013, Vol. 30 Issue 1, p1
Academic Journal
The Philadelphia chromosome (Ph) derives from the balanced translocation between chromosomes 9 and 22. This chromosomal translocation results in the fusion between the 5′ part of the BCR gene, normally located on chromosome 22, and the 3′ part of the ABL gene on chromosome 9 giving origin to a BCR- ABL fusion gene which is transcribed and then translated into a hybrid protein. In general, three breakpoint cluster regions in the BCR gene have been described: major (M-BCR), minor (m-BCR) and micro (μ-BCR). Three main variants of the BCR- ABL gene have been described depending on the length of the sequence of the BCR gene included that encode for the P190, P210, P230 proteins. Most patients (95 %) were found to have P210 protein that resulted from rearrangement in the M-BCR region in the BCR gene and thus gives rise to b2a2 or b3a2 variants. The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. These two variants are associated with distinct clinical types of human leukemias. In this study, we report the frequencies of M- BCR- ABL fusion transcripts in 44 CML patients and we review the data on the correlations between the type of M- BCR/ABL variant and the corresponding sex, age and biological features. Forty-four untreated chronic phase CML patients were studied. The type of BCR- ABL fusion transcripts was determined by reverse transcriptase polymerase chain reaction (RT-PCR). More than half of them showed b3a2 fusion transcript (64 %), while (36 %) showed b2a2 transcript. No patients coexpressed b3a2/b2a2. Correlation between biological data demonstrated that: (a) M- BCR rearrangements were not associated with the sex of the patients. (b) Patients with b3a2 rearrangements were older than patients with b2a2 transcripts. (c) M- BCR rearrangements were influenced neither by the white blood count (WBC) nor with hemoglobin levels. However, platelet level is more elevated in patients with b3a2 transcript (681.2/L vs. 207/L; P = 0.001). In conclusion, we observed significant correlations between age, platelet level and M- BCR- ABL transcript, these observations deserve further investigations.


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