Prognostic significance of expression levels of stem cell regulators MSI2 and NUMB in acute myeloid leukemia.
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Prognostic significance of expression levels of stem cell regulators MSI2 and NUMB in acute myeloid leukemia. / Thol, Felicitas; Winschel, Claudia; Sonntag, Ann-Kathrin; Damm, Frederik; Wagner, Katharina; Chaturvedi, Anuhar; Göhring, Gudrun; Schlegelberger, Brigitte; Lübbert, Michael; Fiedler, Walter; Kirchner, Hartmut; Krauter, Jürgen; Ganser, Arnold; Heuser, Michael.
In: ANN HEMATOL, Vol. 92, No. 3, 3, 2013, p. 315-323.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prognostic significance of expression levels of stem cell regulators MSI2 and NUMB in acute myeloid leukemia.
AU - Thol, Felicitas
AU - Winschel, Claudia
AU - Sonntag, Ann-Kathrin
AU - Damm, Frederik
AU - Wagner, Katharina
AU - Chaturvedi, Anuhar
AU - Göhring, Gudrun
AU - Schlegelberger, Brigitte
AU - Lübbert, Michael
AU - Fiedler, Walter
AU - Kirchner, Hartmut
AU - Krauter, Jürgen
AU - Ganser, Arnold
AU - Heuser, Michael
PY - 2013
Y1 - 2013
N2 - Deregulation of the hematopoietic stem cell (HSC) compartment represents a hallmark of acute myeloid leukemia (AML). Recently, in vivo screening for genes that are involved in the regulation of HSCs has led to the discovery of Musashi-2 (MSI2) as a key regulator of HSCs and as a suppressor of NUMB. In order to analyze the prognostic importance of MSI2 and NUMB expression in AML, MSI2 and NUMB transcript levels from 454 AML patients treated in multicenter trials AML SHG 0199 (ClinicalTrials Identifier NCT00209833) and 0295, and 38 healthy volunteers were analyzed by reverse transcriptase PCR in the context of other molecular markers (NPM1, FLT3, CEBPA, IDH1/IDH2, DNMT3A, NRAS, WT1, KIT, MN1, BAALC, ERG, and WT1). In AML, patients with high MSI2 expression were more likely to be FLT3-ITD positive (P < .001), NPM1 (P < .001), and DNMT3A (P = .003) mutated. Overall survival (OS) was shorter in AML patients with high MSI2 expression (hazard ratio, 1.48; 95 % confidence interval, 1.13-1.95, P = .005). However, relapse-free survival (RFS, P = .15) and complete remission (CR, P = .39) rates were not influenced by MSI2 expression. In multivariate analysis, MSI2 expression remained an independent prognostic factor for OS (P = .03). NUMB expression had no impact on survival (OS, P = .47; RFS, P = .59) and CR rate (P = .39). MSI2 but not NUMB is associated with shorter OS in AML patients and may indicate a more aggressive form of AML.
AB - Deregulation of the hematopoietic stem cell (HSC) compartment represents a hallmark of acute myeloid leukemia (AML). Recently, in vivo screening for genes that are involved in the regulation of HSCs has led to the discovery of Musashi-2 (MSI2) as a key regulator of HSCs and as a suppressor of NUMB. In order to analyze the prognostic importance of MSI2 and NUMB expression in AML, MSI2 and NUMB transcript levels from 454 AML patients treated in multicenter trials AML SHG 0199 (ClinicalTrials Identifier NCT00209833) and 0295, and 38 healthy volunteers were analyzed by reverse transcriptase PCR in the context of other molecular markers (NPM1, FLT3, CEBPA, IDH1/IDH2, DNMT3A, NRAS, WT1, KIT, MN1, BAALC, ERG, and WT1). In AML, patients with high MSI2 expression were more likely to be FLT3-ITD positive (P < .001), NPM1 (P < .001), and DNMT3A (P = .003) mutated. Overall survival (OS) was shorter in AML patients with high MSI2 expression (hazard ratio, 1.48; 95 % confidence interval, 1.13-1.95, P = .005). However, relapse-free survival (RFS, P = .15) and complete remission (CR, P = .39) rates were not influenced by MSI2 expression. In multivariate analysis, MSI2 expression remained an independent prognostic factor for OS (P = .03). NUMB expression had no impact on survival (OS, P = .47; RFS, P = .59) and CR rate (P = .39). MSI2 but not NUMB is associated with shorter OS in AML patients and may indicate a more aggressive form of AML.
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Adolescent
KW - Young Adult
KW - Prognosis
KW - Gene Expression Regulation, Neoplastic
KW - Survival Rate/trends
KW - Hematopoietic Stem Cells/physiology
KW - Leukemia, Myeloid, Acute/diagnosis/metabolism/mortality
KW - Membrane Proteins/biosynthesis
KW - Nerve Tissue Proteins/biosynthesis
KW - RNA-Binding Proteins/biosynthesis
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Adolescent
KW - Young Adult
KW - Prognosis
KW - Gene Expression Regulation, Neoplastic
KW - Survival Rate/trends
KW - Hematopoietic Stem Cells/physiology
KW - Leukemia, Myeloid, Acute/diagnosis/metabolism/mortality
KW - Membrane Proteins/biosynthesis
KW - Nerve Tissue Proteins/biosynthesis
KW - RNA-Binding Proteins/biosynthesis
U2 - 10.1007/s00277-012-1637-5
DO - 10.1007/s00277-012-1637-5
M3 - SCORING: Journal article
C2 - 23233047
VL - 92
SP - 315
EP - 323
JO - ANN HEMATOL
JF - ANN HEMATOL
SN - 0939-5555
IS - 3
M1 - 3
ER -
