Philadelphia-negative (Ph-) chronic myeloid leukemia (CML): comparison with Ph+ CML and chronic myelomonocytic leukemia. The Groupe Francais de Cytogenetique Hematologique

Abstract

To better understand the Philadelphia-negative (Ph-) chronic myeloid leukemia (CML) and its relationships with Philadelphia-positive (Ph+) CML and chronic myelomonocytic leukemia (CMML), a study was undertaken by the Groupe Francais de Cytogenetique Hematologique. Thirty-five Ph- CML patients were investigated and compared with 55 chronic phase Ph+ CML and 100 CMML patients. There were 12 M-BCR positive (M-BCR+) and 23 M-BCR negative (MBCR+) patients. No clinical or biologic differences were found between Ph+ and Ph-, M-BCR+ patients. In the Ph- group, M- BCR+ and M-BCR- patients differed significantly in age (47.7 +/- 6.6 v 67.0 +/- 6.1 years, respectively; P = .001), leukocytosis (153.4 +/- 135.1 v 58.5 +/- 37.7 10(9)/L, P = .002), relative monocytosis (1.8% +/- 1.2% v 5.6% +/- 1.4%, P = .048), absolute basophilia (8.5 +/- 9.7 v 0.9 +/- 1.5 10(9)/L, P = .001), percentage of immature myeloid precursors (IMP) in peripheral blood (29.0% +/- 9.5% v 15.3% +/- 8.1%, P = .001), and percentage of erythroblasts in bone marrow (BM) (6.5% +/- 3.5% v 14.6% +/- 3.6%, P = .001). Karyotypic abnormalities other than the Ph chromosome occurred in 0 of 12 M-BCR- at diagnosis and 7 of 23 M-BCR- Ph- CML (P = .033). None of the 13 investigated BCR- patients had detectable BCR/ABL transcripts using polymerase chain reaction (PCR) and none had an N-RAS mutation. Cytologic findings showed a marked morphologic difference between M-BCR+ and M-BCR- patients, especially in the monocytic lineage. Dysmyelopoietic features in CMML and M-BCR- patients were very similar, and the differences were of quantitative order only. Using four criteria (monocytosis, percentage of IMP, basophilia, and percentage of erythroblasts in BM), patients could be divided into typical and atypical CML and this classification correlated well with molecular findings. We conclude that, while Ph-, M- BCR+, and Ph+ CML are identical diseases, Ph-, M-BCR- CML, and CMML have many similarities and might be only different aspects of a same entity.

Establishment of a novel human myeloid leukaemia cell line (FKH‐1) with t(6;9)(p23;q34) and the expression of dek‐can chimaeric transcript

“…From these observations they proposed that basophilia in the t(6;9) patients might be primarily linked not with the chromosomal abnormality t(6;9) but with the myelodysplasia. Since our patient also had preceeding Ph 1 ‐negative CML with trililneage myelodysplasias, marked basophilia might be linked with myelodysplasia and/or Ph 1 ‐negative CML in which basophilia was a common finding ( Kurzrock et al , 1990 ; Dobrovic et al , 1991 ; Martiat et al , 1991 ), but not with the t(6;9) itself. Since the chromosome change t(6;9) initally appeared at leukaemic transformation, the cells with t(6;9) might have been a minor population at the diagnosis of Ph 1 ‐negative CML, which would have had a growth advantage during acute leukaemic transformation.…”

“…Ph 1 chromosome was negative, and both P210 and P190 BCR/ABL chimaeric mRNA were also negative. The patient was diagnosed as having Ph 1 ‐negative CML ( Kurzrock et al , 1990 ; Dobrovic et al , 1991 ; Martiat et al , 1991 ; Costello et al , 1995 ) or an unclassified chronic myeloproliferative disorder ( Verhoef et al , 1994 ). In June 1993 his disease transformed into overt AML (M4) (WBC 46.8 × 10 9 /l with 37% blasts, 8% basophils and monocytes 5.6 × 10 9 /l).…”

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph‐negative, BCR‐positive patients with chronic myeloid leukemia

“…When investigated by molecular means, some cases show evidence of an M-BCR rearrangement or a BCR-ABL mRNA. T h e remaining cases are Ph-negative cytogenetically and molecularly and show slightly different pathological features and shorter survival (Martiat et al, 1991;Van der Plas et al, 1991).…”

Application of immunophenotypic analysis in distinguishing chronic myelomonocytic leukemia from reactive monocytosis

“…Cytogenetic evidence of clonality is found in only 20% to 40% of CMML cases. (4,5) The morphological differentiation between reactive monocytosis and CMML can be challenging, especially in cases with absent or minimal dysplasia and a normal karyotype. Flow cytometry immunophenotyping is a reliable method for quantitative and qualitative evaluation of hematopoietic cells and plays an increasingly important role in the diagnosis of myelodysplastic syndrome (MDS).…”