High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression DOI Open Access
Linda Resar, Li Luo

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2125 - 2125

Опубликована: Фев. 27, 2025

Patients with chronic, indolent myeloproliferative neoplasms (MPNs) are at risk for transformation to highly lethal leukemia, although targetable mechanisms driving progression remain elusive. We discovered that the High Mobility Group A1 (HMGA1) gene is up-regulated MPN in patients and required evolution into myelofibrosis (MF) or acute myeloid leukemia (AML) preclinical models. HMGA1 encodes epigenetic regulators modulate chromatin state during embryogenesis tissue regeneration. While silenced most differentiated cells, it becomes aberrantly re-expressed JAK2 mutant (JAK2-V617F) MPN, highest levels after secondary MF AML. Here, we review recent work highlighting function progression. Though underlying continue emerge, increasing evidence suggests functions as a "chromatin key" "unlock" regions of genome involved clonal expansion MPN. Together, these findings illuminate driver promising therapeutic target.

Язык: Английский

HMGA1 is a crucial mediator of colon tumorigenesis driven by the loss of APC DOI Creative Commons
Yuxiang Wang,

Mikayla Ybarra,

Zhenghe Wang

и другие.

Journal of Clinical Investigation, Год журнала: 2025, Номер 135(3)

Опубликована: Фев. 2, 2025

Colorectal cancer is the second leading cause of death in United States. The adenomatous polyposis coli (APC) pathway plays a critical role colorectal tumorigenesis, but mechanism not fully understood. In this issue JCI, Luo and colleagues used genetically engineered mouse models to show that high mobility group A (HMGA1) mediator development colon tumors driven by loss Apc gene. HMGA1 activated transcription Achaete-Scute Family BHLH Transcription Factor 2 (ASCL2), which regulated intestinal stemness promoted tumorigenesis.

Язык: Английский

Процитировано

0
High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression DOI Open Access
Linda Resar, Li Luo

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2125 - 2125

Опубликована: Фев. 27, 2025

Patients with chronic, indolent myeloproliferative neoplasms (MPNs) are at risk for transformation to highly lethal leukemia, although targetable mechanisms driving progression remain elusive. We discovered that the High Mobility Group A1 (HMGA1) gene is up-regulated MPN in patients and required evolution into myelofibrosis (MF) or acute myeloid leukemia (AML) preclinical models. HMGA1 encodes epigenetic regulators modulate chromatin state during embryogenesis tissue regeneration. While silenced most differentiated cells, it becomes aberrantly re-expressed JAK2 mutant (JAK2-V617F) MPN, highest levels after secondary MF AML. Here, we review recent work highlighting function progression. Though underlying continue emerge, increasing evidence suggests functions as a "chromatin key" "unlock" regions of genome involved clonal expansion MPN. Together, these findings illuminate driver promising therapeutic target.

Язык: Английский

Процитировано

0