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

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)928-35
Aantal pagina's8
TijdschriftBlood
Volume117
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 20 jan. 2011
Extern gepubliceerdJa

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