Mutations associated with a 17-gene leukemia stem cell score and the score’s prognostic relevance in the context of the European LeukemiaNet classification of acute myeloid leukemia
Marius Bill,
Deedra Nicolet,
Jessica Kohlschmidt,
Christopher J. Walker,
Krzysztof Mrózek,
Ann-Kathrin Eisfeld,
Dimitrios Papaioannou,
Xiaoqing Rong-Mullins,
Zachary Brannan,
Jonathan E. Kolitz,
Bayard L. Powell,
Kellie J. Archer,
Adrienne M. Dorrance,
Andrew J. Carroll,
Richard M. Stone,
John C. Byrd,
Ramiro Garzon,
Clara D. Bloomfield
Affiliations
Marius Bill
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Deedra Nicolet
The Ohio State University Comprehensive Cancer Center, Columbus, OH;Alliance Statistics and Data Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH
Jessica Kohlschmidt
The Ohio State University Comprehensive Cancer Center, Columbus, OH;Alliance Statistics and Data Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH
Christopher J. Walker
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Krzysztof Mrózek
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Ann-Kathrin Eisfeld
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Dimitrios Papaioannou
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Xiaoqing Rong-Mullins
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Zachary Brannan
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Jonathan E. Kolitz
Monter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY
Bayard L. Powell
Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC
Kellie J. Archer
The Ohio State University Comprehensive Cancer Center, Columbus, OH;College of Public Health, The Ohio State University, Columbus, OH
Adrienne M. Dorrance
The Ohio State University Comprehensive Cancer Center, Columbus, OH;Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
Andrew J. Carroll
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL
Richard M. Stone
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
John C. Byrd
The Ohio State University Comprehensive Cancer Center, Columbus, OH;Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
Ramiro Garzon
The Ohio State University Comprehensive Cancer Center, Columbus, OH;Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
Clara D. Bloomfield
The Ohio State University Comprehensive Cancer Center, Columbus, OH;Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
Leukemia stem cells (LSC) are more resistant to standard chemotherapy and their persistence during remission can cause relapse, which is still one of the major clinical challenges in the treatment of acute myeloid leukemia (AML). A better understanding of the mutational patterns and the prognostic impact of molecular markers associated with stemness could lead to better clinical management and improve patients’ outcomes. We applied a previously described 17-gene expression score comprising genes differently expressed between LSC and leukemic bulk blasts, for 934 adult patients with de novo AML, and studied associations of the 17-gene LSC score with clinical data and mutation status of 81 genes recurrently mutated in cancer and leukemia. We found that patients with a high 17-gene score were older and had more mutations. The 17-gene score was found to have a prognostic impact in both younger (aged
