The possible influences of B2A2 and B3A2 BCR/ABL protein structure on thrombopoiesis in chronic myeloid leukaemia

The Philadelphia chromosome, t(9;22)(q34;q11) gives rise more frequently, i n chronic myeloid leukaemia (CML), to two BCR/ ABL chimeric transcripts dif fering only by the absence of 75 nucleotides and defined as b2a2 and b3a2 t ypes, encoding two 210-kDa tyrosine kinase proteins differing only by the a bsence of 25 amino acids coded by the b3 exon. In the present study the two transcripts, detected by RT-PCR in 88 consecutive unselected CML patients, were correlated with haematological findings at diagnosis and with the meg akaryocyte size and frequency by morphometric evaluation of 45 bone marrow biopsies. The secondary structure prediction and hydrophobicity of the b2a2 and b3a2 type BCR/ABL protein were also obtained. The prediction results f or the b3 exon amino acids using GOR IV and NnPredict methods showed a shor t beta strand corresponding to the hydrophobic portion of the peptide. Sign ificantly higher values were found in the platelet count of patients carryi ng b3a2 transcripts. The megakaryocyte size and frequency in bone marrow bi opsies did not show significant differences between the two groups of patie nts. Stratifying the patients on the basis of white blood cell (WBC) count below or above 100 x 10(9)/1 we still had, in both groups, a significant di fference in the platelet count between the b2a2 and b3a2 patients. The poss ible relationships between the structure of b2a2 and b3a2 types of BCR/ABL fused protein and thrombopoiesis are discussed. (C) 2000 Elsevier Science L td. All rights reserved.