MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells

Dina Stroopinsky; Jacalyn Rosenblatt; Keisuke Ito; Heidi Mills; Li Yin; Hasan Rajabi; Baldev Vasir; Turner Kufe; Katarina Luptakova; Jon Arnason; Caterina Nardella; James D. Levine; Robin M. Joyce; Ilene Galinsky; Yoram Reiter; Richard M. Stone; Pier Paolo Pandolfi; Donald Kufe; David Avigan

doi:10.1158/0008-5472.CAN-13-0677

MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells

Dina Stroopinsky, Jacalyn Rosenblatt, Keisuke Ito, Heidi Mills, Li Yin, Hasan Rajabi, Baldev Vasir, Turner Kufe, Katarina Luptakova, Jon Arnason, Caterina Nardella, James D. Levine, Robin M. Joyce, Ilene Galinsky, Yoram Reiter, Richard M. Stone, Pier Paolo Pandolfi, Donald Kufe, David Avigan

Biology

Technion - Israel Institute of Technology

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

Abstract

Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34⁺/lineage^-/ CD38^- cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34⁺ populations as similar results were obtained with leukemic cells from patients with CD34^- disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1^high) led to development of leukemia in NOD-SCID IL2Rgamma^null (NSG) immunodeficient mice. In contrast, MUC1^low cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication.

Original language	English
Pages (from-to)	5569-5579
Number of pages	11
Journal	Cancer Research
Volume	73
Issue number	17
DOIs	https://doi.org/10.1158/0008-5472.CAN-13-0677
State	Published - 1 Sep 2013

UN SDGs

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

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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10.1158/0008-5472.CAN-13-0677

Cite this

Stroopinsky, D., Rosenblatt, J., Ito, K., Mills, H., Yin, L., Rajabi, H., Vasir, B., Kufe, T., Luptakova, K., Arnason, J., Nardella, C., Levine, J. D., Joyce, R. M., Galinsky, I., Reiter, Y., Stone, R. M., Pandolfi, P. P., Kufe, D., & Avigan, D. (2013). MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells. Cancer Research, 73(17), 5569-5579. https://doi.org/10.1158/0008-5472.CAN-13-0677

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title = "MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells",

abstract = "Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34+/lineage-/ CD38- cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34+ populations as similar results were obtained with leukemic cells from patients with CD34- disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1high) led to development of leukemia in NOD-SCID IL2Rgammanull (NSG) immunodeficient mice. In contrast, MUC1low cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication.",

author = "Dina Stroopinsky and Jacalyn Rosenblatt and Keisuke Ito and Heidi Mills and Li Yin and Hasan Rajabi and Baldev Vasir and Turner Kufe and Katarina Luptakova and Jon Arnason and Caterina Nardella and Levine, {James D.} and Joyce, {Robin M.} and Ilene Galinsky and Yoram Reiter and Stone, {Richard M.} and Pandolfi, {Pier Paolo} and Donald Kufe and David Avigan",

year = "2013",

month = sep,

day = "1",

doi = "10.1158/0008-5472.CAN-13-0677",

language = "الإنجليزيّة",

volume = "73",

pages = "5569--5579",

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Stroopinsky, D, Rosenblatt, J, Ito, K, Mills, H, Yin, L, Rajabi, H, Vasir, B, Kufe, T, Luptakova, K, Arnason, J, Nardella, C, Levine, JD, Joyce, RM, Galinsky, I, Reiter, Y, Stone, RM, Pandolfi, PP, Kufe, D & Avigan, D 2013, 'MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells', Cancer Research, vol. 73, no. 17, pp. 5569-5579. https://doi.org/10.1158/0008-5472.CAN-13-0677

TY - JOUR

T1 - MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells

AU - Stroopinsky, Dina

AU - Rosenblatt, Jacalyn

AU - Ito, Keisuke

AU - Mills, Heidi

AU - Yin, Li

AU - Rajabi, Hasan

AU - Vasir, Baldev

AU - Kufe, Turner

AU - Luptakova, Katarina

AU - Arnason, Jon

AU - Nardella, Caterina

AU - Levine, James D.

AU - Joyce, Robin M.

AU - Galinsky, Ilene

AU - Reiter, Yoram

AU - Stone, Richard M.

AU - Pandolfi, Pier Paolo

AU - Kufe, Donald

AU - Avigan, David

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34+/lineage-/ CD38- cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34+ populations as similar results were obtained with leukemic cells from patients with CD34- disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1high) led to development of leukemia in NOD-SCID IL2Rgammanull (NSG) immunodeficient mice. In contrast, MUC1low cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication.

AB - Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34+/lineage-/ CD38- cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34+ populations as similar results were obtained with leukemic cells from patients with CD34- disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1high) led to development of leukemia in NOD-SCID IL2Rgammanull (NSG) immunodeficient mice. In contrast, MUC1low cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication.

UR - http://www.scopus.com/inward/record.url?scp=84883480498&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-13-0677

DO - 10.1158/0008-5472.CAN-13-0677

M3 - مقالة

C2 - 23867470

SN - 0008-5472

VL - 73

SP - 5569

EP - 5579

JO - Cancer Research

JF - Cancer Research

IS - 17

ER -

MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells

Abstract

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