Prospective feasibility of a minimal BH3 profiling assay in acute myeloid leukemia.

BH3 profiling can assess global mitochondrial priming and dependence of leukemic cells on specific BH3 anti-apoptotic proteins such as BCL-2. In acute myeloid leukemia (AML), proof-of-concept prognostic studies have been performed on archived samples variably accounting for molecular genetics. We undertook a single-center feasibility study of a simplified flow-based assay to determine the absolute mitochondrial priming and BCL-2 dependence in consecutive AML patients.

Targeting heterochromatin eliminates chronic myelomonocytic leukemia malignant stem cells through reactivation of retroelements and immune pathways.

Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy affecting the elderly, for which therapeutic options are limited. DNA hypomethylating agents (HMAs) provide transient responses, failing to eradicate the malignant clone. Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization, evidenced by alterations in histone marks H3K9me2 and H3K9me3.

CXCL8 secreted by immature granulocytes inhibits WT hematopoiesis in chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate.

Single-cell sequencing applications in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies with poor prognosis. AML result from the proliferation of immature myeloid cells blocked at a variable stage of differentiation. Beyond inter-patient heterogeneity, AMLs are characterized by genetic and phenotypic intra-patient heterogeneity.