Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival.
Gene expression profiles were examined in 33 adult patients with T-cell acute lymphocytic leukemia (T-ALL). Nonspecific filtering criteria identified 313 genes differentially expressed in the leukemic cells. Hierarchical clustering of samples identified 2 groups that reflected the degree of T-cell differentiation but was not associated with clinical outcome. Comparison between refractory patients and those who responded to induction chemotherapy identified a single gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells and a set of 30 genes that was highly expressed in leukemic cells from patients who achieved complete remission. We next identified 19 genes that were differentially expressed in T-ALL cells from patients who either had a relapse or remained in continuous complete remission. A model based on the expression of 3 of these genes was predictive of duration of remission. The 3-gene model was validated on a further set of T-ALL samples from 18 additional patients treated on the same clinical protocol. This study demonstrates that gene expression profiling can identify a limited number of genes that are predictive of response to induction therapy and remission duration in adult patients with T-ALL.
Chiaretti
Sabina
S
Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Li
Xiaochun
X
Gentleman
Robert
R
Vitale
Antonella
A
Vignetti
Marco
M
Mandelli
Franco
F
Ritz
Jerome
J
Foa
Robin
R
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015996:Survival Rate; D013997:Time Factors; D014407:Tumor Cells, Cultured
D017931:DNA Primers