TY - JOUR
T1 - Neutrophilic-chronic myeloid leukemia
T2 - Low levels of p230 BCR/ABL mRNA and undetectable p230 BCR/ABL protein may predict an indolent course
AU - Verstovsek, Srdan
AU - Lin, Hui
AU - Kantarjian, Hagop
AU - Saglio, Giuseppe
AU - De Micheli, Daniela
AU - Pane, Fabrizio
AU - Garcia-Manero, Guillermo
AU - Intrieri, Mariano
AU - Rotoli, Bruno
AU - Salvatore, Francesco
AU - Guo, Jie Q.
AU - Talpaz, Moshe
AU - Specchia, Giorgina
AU - Pizzolo, Gianni
AU - Liberati, Anna Marina
AU - Cortes, Jorge
AU - Quackenbush, Robert C.
AU - Arlinghaus, Ralph B.
PY - 2002/5/1
Y1 - 2002/5/1
N2 - 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.
AB - 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.
KW - BCR/ABL
KW - Neutrophilic-chronic myeloid leukemia
KW - Philadelphia chromosome
KW - p230
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U2 - 10.1002/cncr.10490
DO - 10.1002/cncr.10490
M3 - Article
C2 - 12015767
AN - SCOPUS:0036569823
SN - 0008-543X
VL - 94
SP - 2416
EP - 2425
JO - Cancer
JF - Cancer
IS - 9
ER -