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

Abstract

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.

BCR-ABL1 transcript types showed distinct laboratory characteristics in patients with chronic myeloid leukemia

“…Regarding the main variables at diagnosis, results in our patient group are similar to those already published (Barboza et al, 2000;Bennour et al, 2013;Smith et al, 2014). In agreement with published data, our study showed a statistically significant association between the e14a2 transcript and high platelet count (Bennour et al, 2013), but also between the e13a2 transcript with high leukocyte count (Hanfstein et al, 2014).…”

“…In agreement with published data, our study showed a statistically significant association between the e14a2 transcript and high platelet count (Bennour et al, 2013), but also between the e13a2 transcript with high leukocyte count (Hanfstein et al, 2014). The statistical analysis for the e13a2/e14a2 was not possible, due to the small number of patients with this transcript (N = 5).…”

“…Meissner et al (1999), Cruz et al (2014), andAl-Achkar et al (2016) found no significant association between the transcript type and various clinical and laboratory parameters. However, the e14a2 transcript has been associated with high platelet count (Inokuchi et al, 1991;Perego et al, 2000;Rosas-Cabral et al, 2003;Bennour et al, 2013) and age at diagnosis (Bennour et al, 2013).…”

The Frequency of BCR-ABL1 Fusion Transcripts in Iranian Patients with Three Different Types of Leukemia

“…The transcript distribution in CML has been reported in European and some other populations with frequencies for b2a2 and b3a2 transcripts being nearly of the order of 40% and 55% [10][11][12][13], which is relatively close to the previous from Iran report [8] and our study. However, a study on an Ecuadorian population, showed very different frequencies: 5% for b3a2 and 95% for b2a2 [6].…”

Fusion Gene BCR-Abl : From Etiopathogenesis to the Management of Chronic Myeloid Leukemia

“…19 Types of breakpoint is related to the clinical manifestation of CML patients. 24 Patients with major breakpoint type is characterized with neoplastic expansion in myeloid and megacaryocytic, as well as differentiation failure and moderate degree of maturation on granulocyte progenitor. Patients who carry minor type BCR-ABL gene showed monocytosis.…”