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±441.3×10(9)/L vs. 440.4±283.4×10(9)/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× 10(9)/L vs. 143.6±96.5×10(9)/L in MDR1((-)) cases; P=0.047]. On performing the analysis only within the MDR1((+)) group, the b(3)a(2) ((+)) cases were characterized with a significantly higher platelets count [908.7±470.1×10(9)/L vs. 472.9±356.1×10(9)/L; P=0.006] and a lower WBC count [85.4±61.2×10(9)/L vs. 130±93.9×10(9)/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.

Keywords: BCR-ABL breakpoint; MDRI gene expression.; b2a2; b3a2; chronic myeloid leukemia.