Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course.
BACKGROUND
Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed.


METHODS
The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature.


RESULTS
Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course.


CONCLUSIONS
Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings.
Verstovsek
Srdan
S
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Lin
Hui
H
Kantarjian
Hagop
H
Saglio
Giuseppe
G
De Micheli
Daniela
D
Pane
Fabrizio
F
Garcia-Manero
Guillermo
G
Intrieri
Mariano
M
Rotoli
Bruno
B
Salvatore
Francesco
F
Guo
Jie Q
JQ
Talpaz
Moshe
M
Specchia
Giorgina
G
Pizzolo
Gianni
G
Liberati
Anna Marina
AM
Cortes
Jorge
J
Quackenbush
Robert C
RC
Arlinghaus
Ralph B
RB
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015467:Leukemia, Neutrophilic, Chronic / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics*; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D014178:Translocation, Genetic
D010455:Peptides; D012333:RNA, Messenger; C042459:p 230; D016044:Fusion Proteins, bcr-abl