miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

Ai Kotani; Daon Ha; James Hsieh; Prakash K Rao; Diana Schotte; Monique L den Boer; Scott A Armstrong; Harvey F Lodish

doi:10.1182/blood-2008-12-191619

miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

Ai Kotani
, Daon Ha
, James Hsieh
, Prakash K Rao
, Diana Schotte
, Monique L den Boer
, Scott A Armstrong
, Harvey F Lodish

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

89 Citations (Scopus)

Abstract

MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

Original language	English
Pages (from-to)	4169-78
Number of pages	10
Journal	Blood
Volume	114
Issue number	19
DOIs	https://doi.org/10.1182/blood-2008-12-191619
Publication status	Published - 5 Nov 2009
Externally published	Yes

Keywords

Binding Sites/genetics
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p27
Dexamethasone/pharmacology
Down-Regulation
Drug Resistance, Neoplasm/genetics
Gene Expression
Glucocorticoids/pharmacology
Humans
Intracellular Signaling Peptides and Proteins/genetics
MicroRNAs/genetics
Myeloid-Lymphoid Leukemia Protein/genetics
Oncogene Proteins, Fusion/genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
RNA, Neoplasm/genetics
Transfection

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10.1182/blood-2008-12-191619

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title = "miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221",

abstract = "MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.",

keywords = "Binding Sites/genetics, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p27, Dexamethasone/pharmacology, Down-Regulation, Drug Resistance, Neoplasm/genetics, Gene Expression, Glucocorticoids/pharmacology, Humans, Intracellular Signaling Peptides and Proteins/genetics, MicroRNAs/genetics, Myeloid-Lymphoid Leukemia Protein/genetics, Oncogene Proteins, Fusion/genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, RNA, Neoplasm/genetics, Transfection",

author = "Ai Kotani and Daon Ha and James Hsieh and Rao, \{Prakash K\} and Diana Schotte and \{den Boer\}, \{Monique L\} and Armstrong, \{Scott A\} and Lodish, \{Harvey F\}",

year = "2009",

month = nov,

day = "5",

doi = "10.1182/blood-2008-12-191619",

language = "English",

volume = "114",

pages = "4169--78",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

number = "19",

}

TY - JOUR

T1 - miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

AU - Kotani, Ai

AU - Ha, Daon

AU - Hsieh, James

AU - Rao, Prakash K

AU - Schotte, Diana

AU - den Boer, Monique L

AU - Armstrong, Scott A

AU - Lodish, Harvey F

PY - 2009/11/5

Y1 - 2009/11/5

N2 - MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

AB - MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

KW - Binding Sites/genetics

KW - Cell Line, Tumor

KW - Cyclin-Dependent Kinase Inhibitor p27

KW - Dexamethasone/pharmacology

KW - Down-Regulation

KW - Drug Resistance, Neoplasm/genetics

KW - Gene Expression

KW - Glucocorticoids/pharmacology

KW - Humans

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - MicroRNAs/genetics

KW - Myeloid-Lymphoid Leukemia Protein/genetics

KW - Oncogene Proteins, Fusion/genetics

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - RNA, Neoplasm/genetics

KW - Transfection

UR - https://www.scopus.com/pages/publications/77950546589

U2 - 10.1182/blood-2008-12-191619

DO - 10.1182/blood-2008-12-191619

M3 - Article

C2 - 19749093

SN - 0006-4971

VL - 114

SP - 4169

EP - 4178

JO - Blood

JF - Blood

IS - 19

ER -

miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

Abstract

Keywords

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