Clinical, morphological, cytogenetic and molecular aspects of a series of Ph-negative chronic myeloid leukemias.
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.
Aurich
J
J
Laboratoire d'Hématologie, CHU Purpan, Toulouse, France.
Duchayne
E
E
Huguet-Rigal
F
F
Bauduer
F
F
Navarro
M
M
Perel
Y
Y
Pris
J
J
Caballin
M R
MR
Dastugue
N
N
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics / Q000648:ultrastructure; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics / Q000648:ultrastructure; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl