Deciphering Acute Myeloid Leukemia Associated Transcription Factors in Human Primary CD34+ Hematopoietic Stem/Progenitor Cells
Abstract
:1. Introduction: AML and Driver Fusion Genes
2. Defined Chimeric Transcription Factors Expand Human CD34+ Progenitors in Ex Vivo Cultures as Single Factors
2.1. KMT2A Rearrangements (KMT2A-r)
2.2. CBF Rearrangements
2.3. NUP98::HOXA9 Rearrangement
2.4. PML::RARA Rearrangement
3. “Two-Hit” Models for Human CD34+ Ex Vivo Progenitor Cell Expansion
4. Synopsis
Author Contributions
Funding
Conflicts of Interest
References
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Genetic Abnormality | Resulting Fusion Gene/Rearrangement |
---|---|
t(8;21) | RUNX1::RUNX1T1 |
t(16;16) or inv(16) | CBFB::MYH11 |
t(6;9) | DEK::NUP214 |
t(3;3) or inv(3) | RPN1::EVI1 |
t(1;22) | RBM15::MRTFA |
t(9;22) | BCR::ABL1 |
t(15;17) | PML::RARA |
t(11q23) | KMT2A (MLL1, MLL)-r |
t(3q26) | MECOM-r |
t(11p15) | NUP98-r |
biallelic mutations of the CEBPA gene | - |
with other defined genetic alterations | - |
Phenotype | Gene | Culture Conditions | References |
---|---|---|---|
Myeloid, CD34+ subpopulation and mature cells | RUNX1::RUNX1T1 | SCF, IL-3, IL-6, GM-CSF, FLT3-L, erythropoietin | [12,13] |
CBFβ::MYH11 | SCF, IL-3, IL-6, FLT3-L, thrombopoietin | [14] | |
KMT2A::AF4 | IL-3, SCF, FLT3-L | [15] | |
BCR::ABL + BMI1 | IL-3, IL-6, G-CSF, SCF, FLT3-L MS5 stromal feeder cells | [16] | |
Myeloid progenitors, no remaining CD34+ subpopulation | KMT2A::AF9 | SCF, IL-3, IL-6, FLT3-L and TPO | [17] |
NUP98::HOXA9 | SCF, FLT3-L, thrombopoietin | [18] | |
Immature granulocyte-macrophage progenitor-like cells | RUNX1 mutations e.g., RUNX1-S291fs300X | IL-3, IL-6, G-CSF, SCF, FLT3-L, erythropoietin | [19] |
Both myeloid and lymphoid progenitors | KMT2A::ENL | IL-3, SCF, FLT3-L, IL-7 | [20] |
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Kreissig, S.; Windisch, R.; Wichmann, C. Deciphering Acute Myeloid Leukemia Associated Transcription Factors in Human Primary CD34+ Hematopoietic Stem/Progenitor Cells. Cells 2024, 13, 78. https://doi.org/10.3390/cells13010078
Kreissig S, Windisch R, Wichmann C. Deciphering Acute Myeloid Leukemia Associated Transcription Factors in Human Primary CD34+ Hematopoietic Stem/Progenitor Cells. Cells. 2024; 13(1):78. https://doi.org/10.3390/cells13010078
Chicago/Turabian StyleKreissig, Sophie, Roland Windisch, and Christian Wichmann. 2024. "Deciphering Acute Myeloid Leukemia Associated Transcription Factors in Human Primary CD34+ Hematopoietic Stem/Progenitor Cells" Cells 13, no. 1: 78. https://doi.org/10.3390/cells13010078