Correlation between the Type of BCR-ABL Transcripts and Blood Cell Counts in Chronic Myeloid Leukemia—A Possible Influence of MDR1 Gene Expression

Abstract

The impact of BCR-ABL mRNA type (b3a2 vs. b2a2) on chronic myeloid leukemia (CML) phenotype is still a subject of controversies. We searched for a correlation between the BCR-ABL transcripts type and CML patients' characteristics, including MDR1 gene expression. Ninety-eight untreated chronic phase CML patients were studied. The type of BCR-ABL fusion transcripts and MDR1 gene expression were determined by reverse transcriptase polymerase chain reaction. B3a2 and b2a2 transcripts were found in 53 [54%] and 44 [45%] patients, respectively. One patient co-expressed b3a2/b2a2 and was excluded from analysis. The only difference in the clinical characteristics between the two groups was the platelets count, that was higher in b3a2(+) patients [791.3±441.3×109/L vs. 440.4±283.4×109/L in b2a2(+); P=0.007]. MDR1 over-expression [MDR1(+)] was observed in 48 patients (49.5%), more frequently in older patients >60 years [71% (24/34) vs. 38% (24/63) in younger; P=0.008], and was associated with a lower white blood cells (WBC) count [105.5±79.8× 109/L vs. 143.6±96.5×109/L in MDR1(−) cases; P=0.047]. On performing the analysis only within the MDR1(+) group, the b3a2(+) cases were characterized with a significantly higher platelets count [908.7±470.1×109/L vs. 472.9±356.1×109/L; P=0.006] and a lower WBC count [85.4±61.2×109/L vs. 130±93.9×109/L; P=0.004) compared to b2a2(+) patients. No similar differences were found between b3a2(+) and b2a2(+) groups with normal MDR1 levels. These results indicate that the type of BCR-ABL transcripts correlates with the hematological parameters of CML, however only in the subgroup of patients characterized by MDR1 over-expression.

Incidence of BCR-ABL transcript variants in patients with chronic myeloid leukemia: Their correlation with presenting features, risk scores and response to treatment with imatinib mesylate

“…[10111213] However, we found higher platelet counts in patients with b2a2 variety of BCR-ABL than in b3a2. A summary of the two patients with e19a2 transcripts is depicted in Table 4.…”

“…Although some of the studies failed to show any correlation between platelet count and BCR-ABL transcript variants;[20] others recognized higher platelet count in patients carrying b3a2[10111213] However almost all the reported studies correlating these two, related higher platelet count in the b3a2 variety our study had revealed otherwise [Table 4]. The other presenting features as Total WBC count, Hemoglobin, hepatomegaly and splenomegaly are within moderate range of discrimination showing the b2a2 population presenting with relative organomegaly and slightly lower hemoglobin as well as lower WBC count.…”

The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

“…Bennour et al found that patients with the e14a2 transcript type were significantly older than patients in the e13a2 group (mean age of 56 years vs 26 years; P = .001). Other studies did not find a correlation between age and transcript types …”

“…Many studies found no association between leukocyte counts and hemoglobin levels at the time of diagnosis and the transcript types . However, in their study, the German investigators demonstrated that patients with the e13a2 transcript had significantly higher baseline median leukocyte counts compared with patients with the e14a2 transcript (88 × 10 9 /L vs 65 × 10 9 /L; P <.001), but no such relationship was shown for hemoglobin levels .…”

Natural course and biology of CML

“…There has been much debate regarding the consequence of a patient expressing either the e13a2 or e14a2 transcript [18]. The position of the BCR breakpoint has been correlated with patient prognosis [19][20][21], platelet count [22][23][24][25] and response to therapy [19,23,26], but there are other reports refuting the importance of the BCR breakpoint [27][28][29][30].…”