Chronic myeloid leukemia (CML) evolves from Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) with unexpected frequency

Int J Hematol. 2023 Mar;117(3):456-462. doi: 10.1007/s12185-022-03463-0. Epub 2022 Oct 1.

Abstract

Myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by overproduction of myeloid-lineage blood cells and potential risk of evolution to acute myeloid leukemia (AML). Chronic myeloid leukemia (CML) is distinct from other MPNs in that its pathophysiology stems from the BCR-ABL fusion protein of the Philadelphia chromosome (Ph +). Though there are known cases of Ph- and Ph + MPNs coexisting in a single patient, overall prevalence has never been quantified in a prospective cohort. Here, we review our center's MPN registry, which shows 0.6% of Ph- MPN patients later developed CML. This development occurred no less than 10 and up to 36 years after Ph- MPN diagnosis. This rate of chronic transformation exceeds what is expected, as the incidence of CML in the United States is 2 per 100,000 people-years. The probability of this CML case rate in an average-risk population is less than 0.001%, suggesting there are shared risk factors between Ph- and Ph + MPNs. We speculate that these risk factors may include exposures, genetic predispositions, or be inherent to disease biology. Abrupt-onset leukocytosis heralded post-MPN CML in all cases here and suggests this salient clinical feature should trigger hematologists to consider this diagnosis and perform appropriate testing.

Keywords: Cancer epidemiology; Chronic myeloid leukemia; JAK2; Myeloproliferative neoplasms.

Publication types

  • Review

MeSH terms

  • Chronic Disease
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / epidemiology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Myeloproliferative Disorders* / diagnosis
  • Myeloproliferative Disorders* / genetics
  • Philadelphia Chromosome
  • Prospective Studies