High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23)

作者：Kuipers Jenny E; Coenen Eva A; Balgobind Brian V; Stary Jan; Baruchel Andre; de Haas Valerie; de Bont Eveline S J M; Reinhardt Dirk; Kaspers Gertjan J L; Cloos Jacqueline; Danen van Oorschot Astrid A; den Boer Monique L; Marschalek Rolf; Meyer Claus; Pieters Rob; Zwaan C Michel; van den Heuvel Eibrink Marry M^*

来源：Blood, 2011, 117(3): 928-935.

DOI：10.1182/blood-2010-05-286138

Pediatric mixed-lineage leukemia (MLL)-rearranged acute monoblastic leukemia with t(9;11)(p22;q23) has a favorable outcome compared with other MLL-rearranged AML. The biologic background for this difference remains unknown. Therefore, we compared gene expression profiles (GEPs; Affymetrix HGU133 + 2.0) of 26 t(9; 11)(p22;q23) patients with 42 other MLL-rearranged AML. patients to identify differentially expressed genes. IGSF4, a cell-cell adhesion molecule, was found to be highly expressed in t(9; 11)(p22; q23) patients, which was confirmed by real-time quantitative polymerase chain reaction and Western blot. IGSF4 expression within t(9;11)(p22;q23) patients was 4.9 times greater in French-American-British morphology classification (FAB)-M5 versus other FAB-types (P = .001). Methylation status investigation showed that high IGSF4-expressing t(9;11)(p22;q23) patients with FAB-M5 have no promoter hypermethylation, whereas all other cases do. Cell-line incubation with demethylating agent decitabine resulted in promoter demethylation and increased expression of IGSF4. Down-regulation of IGSF4 by siRNA did not affect proliferation or drug sensitivity. In a cohort of 79 MLL-rearranged AML cases, we show significant better overall survival for cases with high IGSF4 expression (5-year overall survival 0.70 vs 0.37, P = .03) In conclusion, we identified IGSF4 overexpression to be discriminative for t(9;11)(p22;q23) patients with FAB-M5, regulated partially by promoter methylation and resulting in survival benefit. (Blood.2011;117(3):928-935)

• 出版日期2011-1-20