Increased anti‐apoptotic (Bcl‐2+) and decreased proliferative (Ki‐67+) cell fractions during the different maturation stages of bone marrow cell populations in MDS and AML: The potential diagnostic impact of the Bcl‐2:Ki‐67 ratio

Cytometry Part B Clinical Cytometry, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

The relationship between apoptosis inhibition and cell proliferation was studied during the maturation stages of erythropoiesis, granulopoiesis, monopoiesis in patients with myelodysplastic syndromes (MDS) acute myeloid leukemia (AML). anti-apoptotic proliferative fractions were determined bone marrow aspirates derived from 25 MDS AML compared to 50 nonmalignant cases, using antibodies Bcl-2 Ki-67, respectively. These applied along ten-color flow cytometry markers for three hematopoietic lineages. Next, Bcl-2:Ki-67 ratio as Bcl-2+ Ki-67+ specific lineages, both total different maturation. Bone samples showed a significant increase fraction reduced compartment non-malignant cases. Overall, particularly increased more mature stages, while decreased frequently immature stages. changes varied among erythropoietic process most differences when comparing This difference restricted that granulopoiesis monopoiesis. All lineages encompass small cells (up 10%) concurrently exhibit marker expression. Although displayed considerable variability their index, resulted clear separation malignant Incorporating this combination Ki-67 into study future diagnostic workups may provide important insights biological behavior these blood-borne neoplasms facilitate personalized therapy decisions patients.

Language: Английский

PX-478 induces apoptosis in acute myeloid leukemia under hypoxia by inhibiting the PI3K/AKT/mTOR pathway through downregulation of GBE1

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 230, P. 116620 - 116620

Published: Nov. 9, 2024

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy characterized by limited therapeutic options and pronounced tendency for relapse. PX-478, novel inhibitor of hypoxia-inducible factor 1-alpha (HIF-1α), has demonstrated antitumor activity across various cancer models, but its specific role in AML remains unexplored. This study aimed to explore the potential target mechanism PX-478-induced cell apoptosis. First, PX-478 induced apoptosis vitro under hypoxia via modulation Bcl-2 family activation mitochondria-mediated caspase cascade, exhibiting concentration-dependent effect. Additionally, vivo administration led notable inhibition subcutaneous xenograft growth mice, coupled with increased tumor RNA sequencing cellular studies revealed downregulation PI3K/AKT/mTOR signaling pathway PX-478-treated cells. Consistently, also implicated Furthermore, screening differential genes subsequent experimental verification, Glycogen branching enzyme 1 (GBE1) may be involved We found that inhibiting GBE1 expression cells (siGBE1) In experiments using reduced (shGBE1), treatment did not further downregulate or enhance Re-expression shGBE1 alleviated PX-478- downregulation. conclusion, our findings provide convincing evidence induces through

Language: Английский