The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells

Kelly J. Morgan; Matthew A. Rowley; Stephen M Wiesner; Diane E. Hasz; Brian G Van Ness; David A Largaespada

doi:10.1016/j.leukres.2006.12.015

The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells

Kelly J. Morgan, Matthew A. Rowley, Stephen M Wiesner, Diane E. Hasz, Brian G Van Ness, David A Largaespada

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

8 Scopus citations

Abstract

Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.

Original language	English (US)
Pages (from-to)	1107-1113
Number of pages	7
Journal	Leukemia research
Volume	31
Issue number	8
DOIs	https://doi.org/10.1016/j.leukres.2006.12.015
State	Published - Aug 2007

Bibliographical note

Funding Information:
The Children's Tumor Foundation provided generous support for KJM through the Young Investigator Award. Grants from the National Cancer Institute and the American Cancer Society (to DAL) supported this research. Packaging cells that contained the NF1-GRD retroviral vector were generously provided by Dr. D. Wade Clapp at the Indiana University Medical School.

Keywords

GAP-related domain
Myeloid leukemia
Neurofibromin
Ras

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2006.12.015

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title = "The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells",

abstract = "Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.",

keywords = "GAP-related domain, Myeloid leukemia, Neurofibromin, Ras",

author = "Morgan, {Kelly J.} and Rowley, {Matthew A.} and Wiesner, {Stephen M} and Hasz, {Diane E.} and {Van Ness}, {Brian G} and Largaespada, {David A}",

note = "Funding Information: The Children's Tumor Foundation provided generous support for KJM through the Young Investigator Award. Grants from the National Cancer Institute and the American Cancer Society (to DAL) supported this research. Packaging cells that contained the NF1-GRD retroviral vector were generously provided by Dr. D. Wade Clapp at the Indiana University Medical School. ",

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doi = "10.1016/j.leukres.2006.12.015",

language = "English (US)",

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AU - Morgan, Kelly J.

AU - Rowley, Matthew A.

AU - Wiesner, Stephen M

AU - Hasz, Diane E.

AU - Van Ness, Brian G

AU - Largaespada, David A

N1 - Funding Information: The Children's Tumor Foundation provided generous support for KJM through the Young Investigator Award. Grants from the National Cancer Institute and the American Cancer Society (to DAL) supported this research. Packaging cells that contained the NF1-GRD retroviral vector were generously provided by Dr. D. Wade Clapp at the Indiana University Medical School.

PY - 2007/8

Y1 - 2007/8

N2 - Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.

AB - Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.

KW - GAP-related domain

KW - Myeloid leukemia

KW - Neurofibromin

KW - Ras

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SN - 0145-2126

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JO - Leukemia research

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ER -

The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells

Abstract

Bibliographical note

Keywords

UN SDGs

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