title: Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course.
abstract: 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.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Hui
authors.initials: H
authors.lastname: Lin
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Daniela
authors.initials: D
authors.lastname: De Micheli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Mariano
authors.initials: M
authors.lastname: Intrieri
authors.forename: Bruno
authors.initials: B
authors.lastname: Rotoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.forename: Jie Q
authors.initials: JQ
authors.lastname: Guo
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Gianni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Robert C
authors.initials: RC
authors.lastname: Quackenbush
authors.forename: Ralph B
authors.initials: RB
authors.lastname: Arlinghaus
mesh_terms: 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
chemical_list: D010455:Peptides; D012333:RNA, Messenger; C042459:p 230; D016044:Fusion Proteins, bcr-abl