Table 1.
Genes and processes recently revealed to have roles in both HSC aging and transformation
| Gene | Expression in old vs young HSCs | HSC phenotype | Hematologic malignancy phenotype | Function |
|---|---|---|---|---|
| Selp | HSC aging (RNA and protein38) | Knockout increases hematopoietic regeneration39 | Knockout accelerates leukemogenesis in CML39,40 | Cell adhesion molecule produced by platelets and endothelial cells for leukocyte adhesion38 |
| Nupr1 | HSC aging (RNA38) | Knockout increases HSC quiescence and engraftment potency41 | Targeted inhibition reduces the growth of AML, T-cell ALL, lymphoma, and multiple myeloma cell lines42,43 | High-mobility group protein family member involved in apoptosis, stress response, and cancer progression41 |
| Sema4a | HSC aging (RNA38) | Knockout increases myeloid-biased HSC proliferation and impairs regenerative capacity44 | Knockout impairs multiple myeloma cell growth45 | Binds to surface receptor Plexin-D1, essential for HSC self-renewal and protection from stress44 |
| Cited2 | HSC aging (RNA38) | Knockout depletes functional HSCs in young mice46 | Knockdown decreases AML pathogenesis and induces apoptosis47 | Binding partner of the acetyltransferase CBP/p300 in transcriptional regulation46 |
| Hsf1 | HSC aging (protein48) | Dispensable in young HSCs; knockout impairs hematopoietic regeneration by middle age48 | Knockout impairs initiation and maintenance of AML and T-cell ALL49,50 | Maintains proteostasis and self-renewal in response to stress48 |
| Igf2bp2 | HSC aging (RNA51) | Knockout impairs HSC function in young mice51 | Knockdown inhibits the growth of AML cell lines52 | RNA-binding protein that regulates messenger RNA stability and translation51 |
| Egr1 | HSC aging (RNA53) | Knockout increases HSC cycling and mobilization54 | Tumor suppressor in ALL, CML, and AML55 | Transcription factor that regulates cell growth, differentiation, and depolarization55 |
| Twist1 | HSC aging (RNA56) | Knockout reduces HSC self-renewal and causes myeloid-biased hematopoiesis56 | Knockdown reduces AML cell line proliferation and sensitizes to decitabine57 | Transcription factor essential for embryonic mesoderm development56 |
| Gata2 | No change (RNA38) | Haploinsufficiency promotes HSC proliferation and functional decline58 | Haploinsufficiency causes long latency but aggressive MDS and AML59 | Essential transcription factor for fetal and adult hematopoiesis60 |