Publikationsdatum:
2008-11-16
Beschreibung:
In infant ALL a constellation of features (young age, hyperleukocytosis, extramedullary/CNS disease, CD10− phenotype, MLL translocation, slow early response to treatment) are associated with poor outcome. Despite the frequent MLL translocations, the biologic basis for these features is unknown. In this study, gene expression profiles of leukemia cells from diagnosis were determined in MLL-rearranged infant ALL and relationships were sought between gene expression and clinical covariates. Patients and Methods: Seventeen infants treated on COG protocol CCG 1953 were studied. Features at diagnosis were: age, 0–333 d, median 121 d; WBC count, 10.2–1,286 ×103/μL, median 229 ×103/μL; CD10−, 14, CD10+, 2, CD10 unknown, 1; CNS1 status, 11, CNS2 status, 2, CNS3 status, 4. Eight were alive and 9 were dead at survival times from 41–3384 d. MLL translocations were identified using karyotype, FISH, Southern blot and PCR. Gene expression profiling was performed with Affymetrix HG_U133 Plus2.0 arrays. Pearson’s correlation coefficients and significance levels were computed between age and log-2 transformed expression levels of each probeset. To find associations between gene expression and MLL partner genes with the age effect controlled, linear regression was run using gene expression as the dependent variable and age and partner gene (AF4 v. other) as the independent variable. Similar linear regressions were run for WBC count, CNS status (excluding CNS2) and survival status. Results: PCR identified the MLL partner genes AF4, ENL, AF9, AF10 and EPS15 in 6, 4, 2, 1 and 1 cases, respectively. In 1 case each with t(4;11)(q21;q23) or t(11;19)(q23;p13.3) partner genes were assigned based on karyotype. Another case harbored a t(6;9;11) (q21;p22;q23). Gene expression was affected more by age at diagnosis than any other factor. Remarkably, gene expression analysis by age at diagnosis as a continuous variable showed correlations of 2072 probesets, all but one of which were positive (p
Print ISSN:
0006-4971
Digitale ISSN:
1528-0020
Thema:
Biologie
,
Medizin
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