MYC protein expression is an important prognostic factor in acute myeloid leukemia

Maro Ohanian; Uri Rozovski; Rashmi Kanagal Shamanna; Lynne V. Abruzzo; Sanam Loghavi; Tapan Mahendra Kadia; Andrew Futreal; Kapil Bhalla; Zhuang Zuo; Yang O Huh; Sean M. Post; Peter Ruvolo; Guillermo Garcia-Manero; Michael Andreeff; Steven M Kornblau; Gautam Borthakur; Peter C Hu; L Jeffrey Medeiros; Koichi Takahashi; Marisa J. Hornbaker; Jianhua Zhang; Graciela M. Nogueras-González; Xuelin Huang; Srdan Verstovsek; Zeev Estrov; Sherry Pierce; Farhad Ravandi-Kashani; Hagop M Kantarjian; Carlos E Bueso-Ramos; Jorge E Cortes

doi:10.1080/10428194.2018.1464158

MYC protein expression is an important prognostic factor in acute myeloid leukemia

Maro Ohanian, Uri Rozovski, Rashmi Kanagal Shamanna, Lynne V. Abruzzo, Sanam Loghavi, Tapan Mahendra Kadia, Andrew Futreal, Kapil Bhalla, Zhuang Zuo, Yang O Huh, Sean M. Post, Peter Ruvolo, Guillermo Garcia-Manero, Michael Andreeff, Steven M Kornblau, Gautam Borthakur, Peter C Hu, L Jeffrey Medeiros, Koichi Takahashi, Marisa J. HornbakerJianhua Zhang, Graciela M. Nogueras-González, Xuelin Huang, Srdan Verstovsek, Zeev Estrov, Sherry Pierce, Farhad Ravandi-Kashani, Hagop M Kantarjian, Carlos E Bueso-Ramos, Jorge E Cortes

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Abstract

As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p =.028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p =.042), event-free survival (EFS) (14 versus 6 months; p =.048), and relapse-free survival (RFS) (25 versus 12 months; p =.024). The prognostic impact of MYC-immunopositivity was retained on multivariate analysis of OS, EFS, and RFS. We conclude that MYC immunopositivity is an important prognostic factor in patients with untreated AML, particularly those at higher risk for relapse.

Original language	English (US)
Pages (from-to)	37-48
Number of pages	12
Journal	Leukemia and Lymphoma
Volume	60
Issue number	1
DOIs	https://doi.org/10.1080/10428194.2018.1464158
State	Published - Jan 2 2019

Keywords

Acute myeloid leukemia (AML)
MYC
immunohistochemistry (IHC)

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group
Flow Cytometry and Cellular Imaging Facility
Clinical Trials Office

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10.1080/10428194.2018.1464158

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Ohanian, M., Rozovski, U., Kanagal Shamanna, R., Abruzzo, L. V., Loghavi, S., Kadia, T. M., Futreal, A., Bhalla, K., Zuo, Z., Huh, Y. O., Post, S. M., Ruvolo, P., Garcia-Manero, G., Andreeff, M., Kornblau, S. M., Borthakur, G., Hu, P. C., Medeiros, L. J., Takahashi, K., ... Cortes, J. E. (2019). MYC protein expression is an important prognostic factor in acute myeloid leukemia. Leukemia and Lymphoma, 60(1), 37-48. https://doi.org/10.1080/10428194.2018.1464158

Ohanian, M, Rozovski, U, Kanagal Shamanna, R, Abruzzo, LV, Loghavi, S , Kadia, TM , Futreal, A , Bhalla, K , Zuo, Z, Huh, YO, Post, SM, Ruvolo, P, Garcia-Manero, G , Andreeff, M , Kornblau, SM , Borthakur, G , Hu, PC , Medeiros, LJ , Takahashi, K, Hornbaker, MJ, Zhang, J, Nogueras-González, GM, Huang, X, Verstovsek, S, Estrov, Z, Pierce, S, Ravandi-Kashani, F , Kantarjian, HM , Bueso-Ramos, CE & Cortes, JE 2019, 'MYC protein expression is an important prognostic factor in acute myeloid leukemia', Leukemia and Lymphoma, vol. 60, no. 1, pp. 37-48. https://doi.org/10.1080/10428194.2018.1464158

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title = "MYC protein expression is an important prognostic factor in acute myeloid leukemia",

abstract = "As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p =.028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p =.042), event-free survival (EFS) (14 versus 6 months; p =.048), and relapse-free survival (RFS) (25 versus 12 months; p =.024). The prognostic impact of MYC-immunopositivity was retained on multivariate analysis of OS, EFS, and RFS. We conclude that MYC immunopositivity is an important prognostic factor in patients with untreated AML, particularly those at higher risk for relapse.",

keywords = "Acute myeloid leukemia (AML), MYC, immunohistochemistry (IHC)",

author = "Maro Ohanian and Uri Rozovski and {Kanagal Shamanna}, Rashmi and Abruzzo, {Lynne V.} and Sanam Loghavi and Kadia, {Tapan Mahendra} and Andrew Futreal and Kapil Bhalla and Zhuang Zuo and Huh, {Yang O} and Post, {Sean M.} and Peter Ruvolo and Guillermo Garcia-Manero and Michael Andreeff and Kornblau, {Steven M} and Gautam Borthakur and Hu, {Peter C} and Medeiros, {L Jeffrey} and Koichi Takahashi and Hornbaker, {Marisa J.} and Jianhua Zhang and Nogueras-Gonz{\'a}lez, {Graciela M.} and Xuelin Huang and Srdan Verstovsek and Zeev Estrov and Sherry Pierce and Farhad Ravandi-Kashani and Kantarjian, {Hagop M} and Bueso-Ramos, {Carlos E} and Cortes, {Jorge E}",

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T1 - MYC protein expression is an important prognostic factor in acute myeloid leukemia

AU - Ohanian, Maro

AU - Rozovski, Uri

AU - Kanagal Shamanna, Rashmi

AU - Abruzzo, Lynne V.

AU - Loghavi, Sanam

AU - Kadia, Tapan Mahendra

AU - Futreal, Andrew

AU - Bhalla, Kapil

AU - Zuo, Zhuang

AU - Huh, Yang O

AU - Post, Sean M.

AU - Ruvolo, Peter

AU - Garcia-Manero, Guillermo

AU - Andreeff, Michael

AU - Kornblau, Steven M

AU - Borthakur, Gautam

AU - Hu, Peter C

AU - Medeiros, L Jeffrey

AU - Takahashi, Koichi

AU - Hornbaker, Marisa J.

AU - Zhang, Jianhua

AU - Nogueras-González, Graciela M.

AU - Huang, Xuelin

AU - Verstovsek, Srdan

AU - Estrov, Zeev

AU - Pierce, Sherry

AU - Ravandi-Kashani, Farhad

AU - Kantarjian, Hagop M

AU - Bueso-Ramos, Carlos E

AU - Cortes, Jorge E

PY - 2019/1/2

Y1 - 2019/1/2

N2 - As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p =.028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p =.042), event-free survival (EFS) (14 versus 6 months; p =.048), and relapse-free survival (RFS) (25 versus 12 months; p =.024). The prognostic impact of MYC-immunopositivity was retained on multivariate analysis of OS, EFS, and RFS. We conclude that MYC immunopositivity is an important prognostic factor in patients with untreated AML, particularly those at higher risk for relapse.

AB - As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p =.028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p =.042), event-free survival (EFS) (14 versus 6 months; p =.048), and relapse-free survival (RFS) (25 versus 12 months; p =.024). The prognostic impact of MYC-immunopositivity was retained on multivariate analysis of OS, EFS, and RFS. We conclude that MYC immunopositivity is an important prognostic factor in patients with untreated AML, particularly those at higher risk for relapse.

KW - Acute myeloid leukemia (AML)

KW - MYC

KW - immunohistochemistry (IHC)

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VL - 60

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JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 1

ER -

MYC protein expression is an important prognostic factor in acute myeloid leukemia

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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