Analysis and comparison of clinicohematological parameters and molecular and cytogenetic response of two Bcr/Abl fusion transcripts

Abstract

ABSTRACT. Different forms of p210 are produced by alternative splicing, namely b2a2 and b3a2. There have been many contrasting data establishing a relationship between the two Bcr/Abl transcripts and platelet counts and also response to treatment. However, the data published to date have been on a small group of patients. The aim of the present study was to determine whether there was any difference between clinical and hematological parameters at diagnosis between the two Bcr/Abl fusion transcripts in our population, and whether the two transcripts responded differently or similarly to imatinib treatment. RT-PCR was performed in 202 cases for detection of Bcr/Abl transcripts in newly diagnosed chronic myelogenous leukemia cases in one year. The two transcripts were compared and correlated with clinical, hematological and FISH data and with response to treatment. A total of 138 cases were of b3a2 and 64 were of b2a2 transcript. There was no correlation between the hemato- logical parameters and the type of transcript. There was a significant association of blast crisis with b2a2, especially with myeloid blast crisis. When compared to FISH results, 10% of b3a2 were found to have a significant association with 5'Abl deletion as compared to 3% of b2a2. On analyzing the therapeutic response, we did not find any difference between the two transcripts. In conclusion, our findings confirm that the b3a2 type transcript is not significantly associated with thrombocytosis, that the short transcript, b2a2, occurs with acute phase, i.e., blast crisis, and that there is no difference in treatment response between the two transcripts. However, further studies are required to understand the molecular pathways involved in the Bcr/Abl mechanism.

Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript

“…22 Furthermore, patients with the e14a2 transcript were found to have a higher level of 5'ABL deletions as an additional chromosomal abnormality, when compared to e13a2-expressing patients. 7 Other studies found no correlations with the above, or with any other clinical or hematologic parameters. .…”

“…7 The e14a2 transcript has been correlated with a higher platelet count in both adults 8,10 and children. 21 Additionally it has been associated with a longer chronic phase and survival, possibly related to the less aggressive course of chronic phase in patients with this transcript type.…”

“…[6][7][8][9][10][11][12] However, to our knowledge, only two studies have addressed the effect of transcript type on the clinical outcome of patients treated with imatinib. One small study of 22 patients in Brazil with variable disease status found a significant difference in response to treatment at 6 months (p=0.0347), with e13a2-expressing patients responding better than those expressing e14a2.…”

“…[6][7][8][9][10][11][12] In the imatinib era one small study of 22 patients in different phases of disease suggested that patients with the e13a2 BCR-ABL transcript may be more sensitive to imatinib treatment; 13 while a larger study indicated that patients with e14a2 have a better molecular response to imatinib.…”

Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib

“…6 Regarding hematologic characteristics at diagnosis, the observation of higher platelet counts in the e14a2 group must now be considered in the light of reports to the contrary over the past two decades. 4,7,8 There has still been no evaluation of distinct disease characteristics and the prognostic implications of different p210 BCR-ABL1 transcript types in a larger data set of CML patients on imatinib treatment. In this study, we analyze the long-term molecular, cytogenetic, and clinical outcome of 1105 chronic-phase CML patients receiving an imatinib-based treatment within the randomized German CML Study IV.…”