A new genomic framework to categorize pediatric acute myeloid leukemia

Masayuki Umeda; Jing Ma; Tamara Westover; Yonghui Ni; Guangchun Song; Jamie L. Maciaszek; Michael Rusch; Delaram Rahbarinia; Scott Foy; Benjamin J. Huang; Michael P. Walsh; Priyadarshini Kumar; Yanling Liu; Wenjian Yang; Yiping Fan; Gang Wu; Sharyn D. Baker; Xiaotu Ma; Lu Wang; Todd A. Alonzo; Jeffrey E. Rubnitz; Stanley Pounds; Jeffery M. Klco

doi:10.1038/s41588-023-01640-3

A new genomic framework to categorize pediatric acute myeloid leukemia

Masayuki Umeda, Jing Ma, Tamara Westover, Yonghui Ni, Guangchun Song, Jamie L. Maciaszek, Michael Rusch, Delaram Rahbarinia, Scott Foy, Benjamin J. Huang, Michael P. Walsh, Priyadarshini Kumar, Yanling Liu, Wenjian Yang, Yiping Fan, Gang Wu, Sharyn D. Baker, Xiaotu Ma, Lu Wang, Todd A. AlonzoJeffrey E. Rubnitz, Stanley Pounds, Jeffery M. Klco

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Abstract

Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.

Original language	English
Pages (from-to)	281-293
Number of pages	13
Journal	Nature Genetics
Volume	56
Issue number	2
DOIs	https://doi.org/10.1038/s41588-023-01640-3
State	Published - Feb 2024

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Umeda, M., Ma, J., Westover, T., Ni, Y., Song, G., Maciaszek, J. L., Rusch, M., Rahbarinia, D., Foy, S., Huang, B. J., Walsh, M. P., Kumar, P., Liu, Y., Yang, W., Fan, Y., Wu, G., Baker, S. D., Ma, X., Wang, L., ... Klco, J. M. (2024). A new genomic framework to categorize pediatric acute myeloid leukemia. Nature Genetics, 56(2), 281-293. https://doi.org/10.1038/s41588-023-01640-3

@article{bb4c6ee67bed4bbba1617a9adc72ff2b,

title = "A new genomic framework to categorize pediatric acute myeloid leukemia",

abstract = "Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.",

author = "Masayuki Umeda and Jing Ma and Tamara Westover and Yonghui Ni and Guangchun Song and Maciaszek, {Jamie L.} and Michael Rusch and Delaram Rahbarinia and Scott Foy and Huang, {Benjamin J.} and Walsh, {Michael P.} and Priyadarshini Kumar and Yanling Liu and Wenjian Yang and Yiping Fan and Gang Wu and Baker, {Sharyn D.} and Xiaotu Ma and Lu Wang and Alonzo, {Todd A.} and Rubnitz, {Jeffrey E.} and Stanley Pounds and Klco, {Jeffery M.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = feb,

doi = "10.1038/s41588-023-01640-3",

language = "English",

volume = "56",

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Umeda, M, Ma, J, Westover, T, Ni, Y, Song, G, Maciaszek, JL, Rusch, M, Rahbarinia, D, Foy, S, Huang, BJ, Walsh, MP, Kumar, P, Liu, Y, Yang, W, Fan, Y, Wu, G, Baker, SD, Ma, X, Wang, L, Alonzo, TA, Rubnitz, JE, Pounds, S & Klco, JM 2024, 'A new genomic framework to categorize pediatric acute myeloid leukemia', Nature Genetics, vol. 56, no. 2, pp. 281-293. https://doi.org/10.1038/s41588-023-01640-3

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AU - Umeda, Masayuki

AU - Ma, Jing

AU - Westover, Tamara

AU - Ni, Yonghui

AU - Song, Guangchun

AU - Maciaszek, Jamie L.

AU - Rusch, Michael

AU - Rahbarinia, Delaram

AU - Foy, Scott

AU - Huang, Benjamin J.

AU - Walsh, Michael P.

AU - Kumar, Priyadarshini

AU - Liu, Yanling

AU - Yang, Wenjian

AU - Fan, Yiping

AU - Wu, Gang

AU - Baker, Sharyn D.

AU - Ma, Xiaotu

AU - Wang, Lu

AU - Alonzo, Todd A.

AU - Rubnitz, Jeffrey E.

AU - Pounds, Stanley

AU - Klco, Jeffery M.

PY - 2024/2

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N2 - Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.

AB - Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.

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A new genomic framework to categorize pediatric acute myeloid leukemia

Abstract

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