Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML.
Although most patients with chronic myeloid leukemia (CML) have the same initial molecular abnormality, the BCR-ABL fusion gene, the duration of chronic phase (CP) varies widely. To identify the possible molecular basis of this heterogeneity, we studied CD34+ cells collected at diagnosis from 68 patients with CML-CP. By using oligonucleotide microarray screening, we performed gene-expression profiling on 2 subsets of patients, one comprising patients with an "aggressive disease" who developed blastic transformation (BT) within 3 years of diagnosis (n = 10) and, at the other extreme, patients with an "indolent disease" whose BT occurred 7 or more years from diagnosis (n = 9). This screening revealed 20 genes differentially expressed in patients with aggressive and indolent disease, which were validated by quantitative reverse transcriptase/polymerase chain reaction (Q-RT/PCR). A multivariate Cox regression model identified the combination of low CD7 expression with high expression of proteinase 3 or elastase as associated with longer survival in the complete cohort of 68 patients. This differential pattern of gene expression probably reflects the intrinsic heterogeneity of the disease; if so, assessing expression levels of selected genes at diagnosis may be valuable in predicting duration of survival in patients treated with imatinib and the newer tyrosine kinase inhibitors.
Yong
Agnes S M
AS
Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, United Kingdom.
Szydlo
Richard M
RM
Goldman
John M
JM
Apperley
Jane F
JF
Melo
Junia V
JV
D018952:Antigens, CD34; D019011:Antigens, CD7 / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000473:pathology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D053146:Myeloblastin; D010196:Pancreatic Elastase / Q000235:genetics*; D011379:Prognosis; D012044:Regression Analysis; D012697:Serine Endopeptidases / Q000235:genetics*; D015996:Survival Rate
D018952:Antigens, CD34; D019011:Antigens, CD7; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D053146:Myeloblastin