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

doi:10.1182/blood-2010-05-286138

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

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	928-35
Number of pages	8
Journal	Blood
Volume	117
Issue number	3
DOIs	https://doi.org/10.1182/blood-2010-05-286138
Publication status	Published - 20 Jan 2011
Externally published	Yes

Keywords

Adolescent
Azacitidine/analogs & derivatives
Blotting, Western
Cell Adhesion Molecule-1
Cell Adhesion Molecules/genetics
Cell Line, Tumor
Child
Child, Preschool
Chromosomes, Human, Pair 11/genetics
Chromosomes, Human, Pair 9/genetics
DNA Methylation/drug effects
Decitabine
Enzyme Inhibitors/pharmacology
Female
Gene Expression Profiling
Gene Expression Regulation, Leukemic/drug effects
HL-60 Cells
Humans
Immunoglobulins/genetics
Infant
Infant, Newborn
Leukemia, Monocytic, Acute/genetics
Male
Oligonucleotide Array Sequence Analysis
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Survival Analysis
Translocation, Genetic

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10.1182/blood-2010-05-286138

Cite this

Kuipers, J. E., Coenen, E. A., Balgobind, B. V., Stary, J., Baruchel, A., de Haas, V., de Bont, E. S. J. M., Reinhardt, D., Kaspers, G. J. L., Cloos, J., Danen-van Oorschot, A. A., den Boer, M. L., Marschalek, R., Meyer, C., Pieters, R., Zwaan, C. M., & van den Heuvel-Eibrink, M. M. (2011). High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23). Blood, 117(3), 928-35. https://doi.org/10.1182/blood-2010-05-286138

@article{fab49e7f54e744ccadb0563147932f7d,

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

abstract = "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.",

keywords = "Adolescent, Azacitidine/analogs & derivatives, Blotting, Western, Cell Adhesion Molecule-1, Cell Adhesion Molecules/genetics, Cell Line, Tumor, Child, Child, Preschool, Chromosomes, Human, Pair 11/genetics, Chromosomes, Human, Pair 9/genetics, DNA Methylation/drug effects, Decitabine, Enzyme Inhibitors/pharmacology, Female, Gene Expression Profiling, Gene Expression Regulation, Leukemic/drug effects, HL-60 Cells, Humans, Immunoglobulins/genetics, Infant, Infant, Newborn, Leukemia, Monocytic, Acute/genetics, Male, Oligonucleotide Array Sequence Analysis, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Survival Analysis, Translocation, Genetic",

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

year = "2011",

month = jan,

day = "20",

doi = "10.1182/blood-2010-05-286138",

language = "English",

volume = "117",

pages = "928--35",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

number = "3",

}

Kuipers, JE, Coenen, EA, Balgobind, BV, Stary, J, Baruchel, A, de Haas, V, de Bont, ESJM, Reinhardt, D, Kaspers, GJL, Cloos, J, Danen-van Oorschot, AA, den Boer, ML, Marschalek, R, Meyer, C, Pieters, R , Zwaan, CM & van den Heuvel-Eibrink, MM 2011, 'High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23)', Blood, vol. 117, no. 3, pp. 928-35. https://doi.org/10.1182/blood-2010-05-286138

TY - JOUR

T1 - High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23)

AU - Kuipers, Jenny E

AU - Coenen, Eva A

AU - Balgobind, Brian V

AU - Stary, Jan

AU - Baruchel, Andre

AU - de Haas, Valerie

AU - de Bont, Eveline S J M

AU - Reinhardt, Dirk

AU - Kaspers, Gertjan J L

AU - Cloos, Jacqueline

AU - Danen-van Oorschot, Astrid A

AU - den Boer, Monique L

AU - Marschalek, Rolf

AU - Meyer, Claus

AU - Pieters, Rob

AU - Zwaan, C Michel

AU - van den Heuvel-Eibrink, Marry M

PY - 2011/1/20

Y1 - 2011/1/20

N2 - 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.

AB - 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.

KW - Adolescent

KW - Azacitidine/analogs & derivatives

KW - Blotting, Western

KW - Cell Adhesion Molecule-1

KW - Cell Adhesion Molecules/genetics

KW - Cell Line, Tumor

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 11/genetics

KW - Chromosomes, Human, Pair 9/genetics

KW - DNA Methylation/drug effects

KW - Decitabine

KW - Enzyme Inhibitors/pharmacology

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Leukemic/drug effects

KW - HL-60 Cells

KW - Humans

KW - Immunoglobulins/genetics

KW - Infant

KW - Infant, Newborn

KW - Leukemia, Monocytic, Acute/genetics

KW - Male

KW - Oligonucleotide Array Sequence Analysis

KW - RNA Interference

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Survival Analysis

KW - Translocation, Genetic

U2 - 10.1182/blood-2010-05-286138

DO - 10.1182/blood-2010-05-286138

M3 - Article

C2 - 21045196

SN - 0006-4971

VL - 117

SP - 928

EP - 935

JO - Blood

JF - Blood

IS - 3

ER -

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

Abstract

Keywords

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