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

Srdan Verstovsek, Hui Lin, Hagop Kantarjian, Giuseppe Saglio, Daniela De Micheli, Fabrizio Pane, Guillermo Garcia-Manero, Mariano Intrieri, Bruno Rotoli, Francesco Salvatore, Jie Q. Guo, Moshe Talpaz, Giorgina Specchia, Gianni Pizzolo, Anna Marina Liberati, Jorge Cortes, Robert C. Quackenbush, Ralph B. Arlinghaus

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48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2416-2425
Number of pages10
JournalCancer
Volume94
Issue number9
DOIs
StatePublished - May 1 2002

Keywords

  • BCR/ABL
  • Neutrophilic-chronic myeloid leukemia
  • Philadelphia chromosome
  • p230

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Verstovsek, S., Lin, H., Kantarjian, H., Saglio, G., De Micheli, D., Pane, F., Garcia-Manero, G., Intrieri, M., Rotoli, B., Salvatore, F., Guo, J. Q., Talpaz, M., Specchia, G., Pizzolo, G., Liberati, A. M., Cortes, J., Quackenbush, R. C., & Arlinghaus, R. B. (2002). Neutrophilic-chronic myeloid leukemia: Low levels of p230 BCR/ABL mRNA and undetectable p230 BCR/ABL protein may predict an indolent course. Cancer, 94(9), 2416-2425. https://doi.org/10.1002/cncr.10490