The spectrum of myeloid disorders ranges from aplastic bone marrow failure characterized by an empty bone marrow completely lacking in hematopoiesis to acute myeloid leukemia in which the marrow space is replaced by undifferentiated leukemic blasts. Recent advances in the capacity to sequence bulk tumor population as well as at a single-cell level has provided significant insight into the stepwise process of transformation to acute myeloid leukemia. Using models of progression in the context of germ line predisposition (trisomy 21, GATA2 deficiency, and SAMD9/9L syndrome), premalignant states (clonal hematopoiesis and clonal cytopenia of unknown significance), and myelodysplastic syndrome, we review the mechanisms of progression focusing on the hierarchy of clonal mutation and potential roles of transcription factor alterations, splicing factor mutations, and the bone marrow environment in progression to acute myeloid leukemia. Despite major advances in our understanding, preventing the progression of these disorders or treating them at the acute leukemia phase remains a major area of unmet medical need.
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May 30, 2024
Malignant progression of preleukemic disorders
Trent Hall,
Trent Hall
1Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN
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Sandeep Gurbuxani,
Sandeep Gurbuxani
2Section of Hematopathology, Department of Pathology, University of Chicago, Chicago, IL
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John D. Crispino
John D. Crispino
1Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN
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Blood (2024) 143 (22): 2245–2255.
Article history
Submitted:
September 27, 2023
Accepted:
February 29, 2024
First Edition:
March 18, 2024
Citation
Trent Hall, Sandeep Gurbuxani, John D. Crispino; Malignant progression of preleukemic disorders. Blood 2024; 143 (22): 2245–2255. doi: https://doi.org/10.1182/blood.2023020817
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May 30 2024
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