Biomaterial Database

High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23). 2011

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

Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.

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.

UI	MeSH Term	Description	Entries
D007136	Immunoglobulins	Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.	Globulins, Immune,Immune Globulin,Immune Globulins,Immunoglobulin,Globulin, Immune
D007223	Infant	A child between 1 and 23 months of age.	Infants
D007231	Infant, Newborn	An infant during the first 28 days after birth.	Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007948	Leukemia, Monocytic, Acute	An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.	Leukemia, Monoblastic, Acute,Leukemia, Myeloid, Acute, M5,Leukemia, Myeloid, Schilling-Type,Monoblastic Leukemia, Acute,Monocytic Leukemia, Acute,Myeloid Leukemia, Acute, M5,Myeloid Leukemia, Schilling-Type,Leukemia, Acute Monocytic,Leukemia, Myeloid, Schilling Type,Acute Monoblastic Leukemia,Acute Monoblastic Leukemias,Acute Monocytic Leukemia,Acute Monocytic Leukemias,Leukemia, Schilling-Type Myeloid,Leukemias, Acute Monoblastic,Leukemias, Acute Monocytic,Monoblastic Leukemias, Acute,Monocytic Leukemias, Acute,Myeloid Leukemia, Schilling Type,Schilling-Type Myeloid Leukemia
D008297	Male		Males
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children
D002880	Chromosomes, Human, Pair 11	A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.	Chromosome 11
D002899	Chromosomes, Human, Pair 9	A specific pair of GROUP C CHROMSOMES of the human chromosome classification.	Chromosome 9
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme