Neutrophilic-chronic myeloid leukemia: Low levels of p230 BCR/ABL mRNA and undetectable p230 BCR/ABL protein may predict an indolent course

BACKGROUND. Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed. METHODS. The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature. RESULTS. Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course. CONCLUSIONS. Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings.