arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by...

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Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones, Tracey Perry, Andrew Beggs, Elena Odintsova, Justin Loke, Guy Pratt, Kin Pong U, Anthony Lo, Margaret Ng, Pamela Kearns, Paul Cheng, and Carmela De Santo Blood Volume 125(15):2386-2396 April 9, 2015 ©2015 by American Society of Hematology

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BCT-100 arginine depletion reduces the number of viable AML blasts in vitro and in vivo. Francis Mussai et al. Blood 2015;125: ©2015 by American Society of Hematology

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Page 1: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones, Tracey Perry, Andrew Beggs, Elena Odintsova, Justin Loke, Guy Pratt, Kin Pong U, Anthony Lo,

Margaret Ng, Pamela Kearns, Paul Cheng, and Carmela De Santo

BloodVolume 125(15):2386-2396

April 9, 2015

©2015 by American Society of Hematology

Page 2: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

AML blasts are auxotrophic for arginine.

Francis Mussai et al. Blood 2015;125:2386-2396

©2015 by American Society of Hematology

Page 3: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

BCT-100 arginine depletion reduces the number of viable AML blasts in vitro and in vivo.

Francis Mussai et al. Blood 2015;125:2386-2396

©2015 by American Society of Hematology

Page 4: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

BCT-100 is cytotoxic against primary blasts from patients.

Francis Mussai et al. Blood 2015;125:2386-2396

©2015 by American Society of Hematology

Page 5: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

BCT-100 depletes arginine intracellularly.

Francis Mussai et al. Blood 2015;125:2386-2396

©2015 by American Society of Hematology

Page 6: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

BCT-100 halts proliferation and cell cycle arrest.

Francis Mussai et al. Blood 2015;125:2386-2396

©2015 by American Society of Hematology

Page 7: Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target by Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones,

BCT-100 induced cell cycle arrest leads to necrotic cell death.

Francis Mussai et al. Blood 2015;125:2386-2396

©2015 by American Society of Hematology