P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia?

Leukemia. 1994 Jan;8(1):208-11.

Abstract

Two-thirds of patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukaemia (ALL) have a breakpoint in the minor breakpoint cluster region (m-bcr) of the BCR gene, which results in an e1a2 transcript and a P190BCR-ABL fusion protein. This type of genomic rearrangement occurs very rarely in chronic myeloid leukaemia (CML); it has been reported in only four cases. We describe here a fifth case of P190 CML in which the cytomorphological characteristics were intermediate between CML and chronic myelomonocytic leukaemia (CMML). This case, and the four reported previously, had a consistent and significant monocytosis with a low neutrophil/monocyte ratio in the peripheral blood, resembling CMML. On the other hand, they also had a high percentage of circulating immature granulocytes, basophilia and low neutrophil alkaline phosphatase (NAP) score, which are more commonly found in classical CML. Thus, P190 CML may be a specific form of CML, in which the myeloproliferative process includes the monocytic, as well as the granulocytic lineage. Since the molecular defect in CML is thought to involve a pluripotent stem cell, the different effects of P210BCR-ABL and P190BCR-ABL in CML must reflect the somewhat wider spectrum of activity of the P190BCR-ABL. Other patients with atypical CML or CMML who lack a Ph chromosome may also have an m-bcr breakpoint which would not be detected on standard Southern blots, but which would be detectable by polymerase chain reaction amplification of reverse transcribed RNA.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Southern
  • DNA Restriction Enzymes / metabolism
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression / genetics
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelomonocytic, Chronic / genetics*
  • Leukemia, Myelomonocytic, Chronic / pathology
  • Male
  • Polymerase Chain Reaction / methods

Substances

  • DNA, Neoplasm
  • Fusion Proteins, bcr-abl
  • DNA Restriction Enzymes