Clinical, morphological, cytogenetic and molecular aspects of a series of ph-negative chronic myeloid leukemias

J. Aurich, E. Duchayne, F. Huguet-Rigal, F. Bauduer, M. Navarro, Y. Perel, J. Pris, M. R. Caballin, N. Dastugue

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18 Citations (Scopus)


Clinical, morphological, cytogenetic and molecular (fluorescence in situ hybridization and RT-PCR) data were analyzed in twelve Philadelphia negative chronic myeloid leukemias (Ph-negative CMLs). Four patients were classified as BCR-positive. A standard b2a2 or b3a2 transcript was found, and the BCR- ABL hybrid gene was located on the 22q11 band in three cases and on the 1p35 band in one case with a t(1;9)(p35;q34). All were classified as typical chronic granulocytic leukemia (CGL) according to the French-American-British (FAB) morphological guidelines. Responses to therapy were evaluated by FISH in the four patients, and proved to be poorer than in Ph-positive CMLs. Eight BCR-negative patients were identified. They could be characterized by an older age, a less proliferative form of disease than the BCR-positive patients, and a frequent (six out of eight) abnormal karyotype. The FAB classification identified four CGLs and four atypical CMLs (aCML). A normal karyotype was more frequent in the patients classified as CGL whereas all the aCMLs had a chromosomal abnormality. Three patients had chromatin clumping and this morphologic feature was associated with trisomy 8 in two. No correlation between the cytogenetic, morphologic and the clinical data were found. Five patients had poor tolerance to therapy with a frequent occurrence of bone marrow failure and hemorragic syndrome, whereas three patients responded to a standard treatment of CML. Our study reinforces previous data on Ph-negative BCR-positive CMLs and emphasizes the difficulty in correlating clinical, morphologic, cytogenetic data in Ph-negative BCR-negative CMLs. However, our data also argue in favor of the existence of true Ph-negative BCR-negative CMLs and suggest that some of them can respond to a standard treatment of CML.
Original languageEnglish
Pages (from-to)149-158
JournalHematology and Cell Therapy
Issue number4
Publication statusPublished - 1 Aug 1998


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