hu128.1, a humanized antibody targeting transferrin receptor 1, blocks erythroleukemia growth in xenograft mouse models.

Not available.

Rocaglamide reprograms glucose metabolism in erythroleukemic cells via c-MYC transcriptional regulation of TXNIP and HK2.

Ethnopharmacological Relevance: The theory of traditional Chinese medicine (TCM) views leukemia as an imbalance between cell growth and death mainly caused by blood stasis. Medicinal plants Aglaia Lour. (family Meliaceae) are traditionally used as folk medicine in China.

JK-1, a useful erythroleukemic cell line model to study a controlled erythroid differentiation from progenitors to terminal erythropoiesis.

New hematopoietic cell models have recently emerged through immortalization of CD34 cells to study and understand various molecular mechanisms of erythropoiesis. Here, we characterize the JK-1 CML-derived cell line, previously shown to spontaneously differentiate without cytokines. Using an epigenetic differentiation inhibitor that keeps JK-1 in an early differentiation phase, we characterized 2 progenitor stages: BFU-E JK-1 and CFU-E JK-1 with CD34+/CD36- and CD34-/CD36 + phenotypes respectively.

A natural acylphloroglucinol exerts anti-erythroleukemia effects via targeting STAT3 and p38-MAPK, and inhibiting PI3K/AKT/mTOR signaling pathway.

Erythroleukemia, a subtype of acute myeloid leukemia (AML), is a life-threatening malignancy that affects the blood and bone marrow. Despite the availability of clinical treatments, the complex pathogenesis of the disease and the severe side effects of chemotherapy continue to impede therapeutic progress in leukemia. In this study, we investigated the antitumor activity of L76, an acylphloroglucinol compound derived from Callistemon salignus DC.

HDAC7 is a potential therapeutic target in acute erythroid leukemia.

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance.

Bi-functional CpG-STAT3 decoy oligonucleotide triggers multilineage differentiation of acute myeloid leukemia in mice.

Acute myeloid leukemia (AML) cells resist differentiation stimuli despite high expression of innate immune receptors, such as Toll-like receptor 9 (TLR9). We previously demonstrated that targeting Signal Transducer and Activator of Transcription 3 (STAT3) using TLR9-targeted decoy oligodeoxynucleotide (CpG-STAT3d) increases immunogenicity of human and mouse AML cells. Here, we elucidated molecular mechanisms of inv(16) AML reprogramming driven by STAT3-inhibition/TLR9-activation .

CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors.

The specification of megakaryocytic (Mk) or erythroid (E) lineages from primary human megakaryocytic-erythroid progenitors (MEPs) is crucial for hematopoietic homeostasis, yet the underlying mechanisms regulating fate specification remain elusive. In this study, we identify RUNX1 as a key modulator of gene expression during MEP fate specification. Overexpression of RUNX1 in primary human MEPs promotes Mk specification, whereas pan-RUNX inhibition favors E specification.

Marine derived macrolide bryostatin 4 inhibits the TGF-β signaling pathway against acute erythroleukemia.

Purpose: Acute erythroleukemia (AEL) is a rare and highly aggressive subtype of acute myeloid leukemia (AML) with an extremely poor prognosis when treated with available drugs. Therefore, new investigational agents capable of inducing remission are urgently required.

Methods: Bioinformatics analysis, western blot and qRT-PCR were used to reveal the potential biological mechanism of bryostatin 4 (B4), an antineoplastic macrolide derived from the marine bryozoan Bugula neritina.

MLL-AF9 regulates transcriptional initiation in mixed lineage leukemic cells.

Mixed lineage leukemia-fusion proteins (MLL-FPs) are believed to maintain gene activation and induce MLL through aberrantly stimulating transcriptional elongation, but the underlying mechanisms are incompletely understood. Here, we show that both MLL1 and AF9, one of the major fusion partners of MLL1, mainly occupy promoters and distal intergenic regions, exhibiting chromatin occupancy patterns resembling that of RNA polymerase II in HEL, a human erythroleukemia cell line without MLL1 rearrangement. MLL1 and AF9 only coregulate over a dozen genes despite of their co-occupancy on thousands of genes.

ERG Regulates Lymphatic Vessel Specification Genes and Its Deficiency Impairs Wound Healing-Associated Lymphangiogenesis.

Objective: Rarefaction of blood and lymphatic vessels in the skin has been reported in systemic sclerosis (SSc) (scleroderma). E26 transformation-specific-related factor (ERG) and Friend leukemia virus-induced erythroleukemia 1 (FLI-1) are important regulators of angiogenesis, but their role in lymphatic vasculature is lesser known. The goal of this study was to determine the role of ERG and FLI-1 in postnatal lymphangiogenesis and SSc lymphatic system defects.

The ETO2 transcriptional cofactor maintains acute leukemia by driving a MYB/EP300-dependent stemness program.

Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well-established repressive activity, ETO2 directly activates transcription of MYB, among other genes.

GPS2 promotes erythroid differentiation in K562 erythroleukemia cells primarily via NCOR1.

G protein pathway suppressor 2 (GPS2) has been shown to play a pivotal role in human and mouse definitive erythropoiesis in an EKLF-dependent manner. However, whether GPS2 affects human primitive erythropoiesis is still unknown. This study demonstrated that GPS2 positively regulates erythroid differentiation in K562 cells, which have a primitive erythroid phenotype.