ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling

Article Biochemistry & Molecular Biology

DRAM-4 and DRAM-5 are compensatory regulators of autophagy and cell survival in nutrient-deprived conditions

Valentin J. A. Barthet et al.

Summary: DRAM-4 and DRAM-5 are nutrient-responsive members of the DRAM family that exhibit interconnected roles in the regulation of autophagy and cell survival under nutrient-deprived conditions.

FEBS JOURNAL (2022)

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Article Oncology

CDK19 regulates the proliferation of hematopoietic stem cells and acute myeloid leukemia cells by suppressing p53-mediated transcription of p21

Zihao Zhang et al.

Summary: CDK19 is involved in the regulation of HSC and AML cell proliferation via the p53-p21 pathway.

LEUKEMIA (2022)

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Article Oncology

Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia

Mark B. Leick et al.

Summary: This study demonstrates the development of an enhanced CD70-targeted CAR using orthogonal approaches to improve binding avidity and expansion of CAR-T cells, showing increased in vivo activity in AML models.

CANCER CELL (2022)

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Article Oncology

PU.1 and MYC transcriptional network defines synergistic drug responses to KIT and LSD1 inhibition in acute myeloid leukemia

Brittany M. Curtiss et al.

Summary: Combination inhibition of KIT and LSD1 can improve the therapeutic response in KIT-mutant AML by driving cell cycle exit through eviction of MYC and PU.1. The addition of an LSD1 inhibitor can reverse early adaptive changes in kinase signaling following KIT inhibition by modulating the GSK3a/b axis. These findings provide a rationale for evaluating the efficacy of KIT and LSD1 inhibition in KIT-mutant AML patients.

LEUKEMIA (2022)

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Article Oncology

Leukotrienes promote stem cell self-renewal and chemoresistance in acute myeloid leukemia

Alec W. Stranahan et al.

Summary: Acute myeloid leukemia (AML) is associated with high relapse rates and poor clinical outcomes. This study identifies ALOX5 as a resistance gene to anthracycline-based therapy in AML and suggests that inhibiting ALOX5 could enhance therapeutic efficacy in AML.

LEUKEMIA (2022)

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Review Physiology

RHO GTPase SIGNALING IN CANCER PROGRESSION AND DISSEMINATION

Eva Crosas-Molist et al.

Summary: This review examines the role of Rho GTPase signaling in different stages of cancer progression, highlighting its importance in tumor initiation, proliferation, and metastasis, as well as its involvement in cell migration, interaction with the tumor microenvironment, and inflammation regulation.

PHYSIOLOGICAL REVIEWS (2022)

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Article Medicine, Research & Experimental

DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD

Jie Tan et al.

Summary: In this study, the expression, role, and mechanism of DRAM1 in alcohol-related liver disease (ALD) were investigated. The results showed that DRAM1 was significantly increased in the liver tissues of mice at the early stage of alcohol treatment. DRAM1 knockout reduced the symptoms of ALD, while liver-specific overexpression of DRAM1 aggravated them. Furthermore, ethanol-induced DRAM1 of hepatic cells increased extracellular vesicles (EVs) enriched with pyruvate kinase M2 (PKM2) and promoted macrophage activation.

MOLECULAR THERAPY-NUCLEIC ACIDS (2022)

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Editorial Material Hematology

Transplant in older adults with AML: genomic wheat and chaff

Sylvie D. Freeman et al.

Summary: In this study, the authors found that molecular persistence in remission does not predict posttransplant outcomes after adjusting for specific baseline molecular and clinical variables in older adults with AML.

BLOOD (2022)

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Article Multidisciplinary Sciences

Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios

Kun-Yin Qiu et al.

Summary: This study explores the relationship between FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identifies an optimal threshold value, highlighting the importance of individualized treatment for pediatric AML.

NATURE COMMUNICATIONS (2022)

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Letter Medicine, General & Internal

Ivosidenib and Azacitidine in IDH1-Mutated AML

Manuel D. Gil-Sierra et al.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Hematology

P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3

Wenli Feng et al.

Summary: High expression of P2X7 is correlated with worse survival outcomes in AML, especially in MLL-rearranged AML. P2X7 accelerates the progression of AML by promoting cell proliferation and increasing leukemia stem cells; P2X7 may contribute to leukemia and solid tumor progression through the P2X7-Pbx3 pathway.

HAEMATOLOGICA (2021)

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Article Oncology

Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence

Cihangir Duy et al.

Summary: The study revealed that primary AML cells can enter a senescence-like phenotype after chemotherapy, leading to a decrease in leukemia stem cells and an increase in subpopulations with senescence-like cells. Moreover, ATR inhibitors can transiently impair the persistence of AML cells.

CANCER DISCOVERY (2021)

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Article Medicine, Research & Experimental

Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models

Xiaoxiao He et al.

Summary: The study revealed that in a mouse model of acute myeloid leukemia, ATP levels were increased in bone marrow niches, LICs preferred niches with high ATP levels, and P2X7 channel played a crucial role in this process, affecting homing, self-renewal, and functionality of LICs.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Cell Biology

Functional reconstruction of human AML reveals stem cell origin and vulnerability of treatment-resistant MLL-rearranged leukemia

Bernd B. Zeisig et al.

Summary: This study identified two distinct origins of human LSCs for MLL-AML and their role in mediating chemoresistance, as well as a potential therapeutic avenue for stem cell-associated treatment resistance by repurposing the well-tolerated antidiarrhea drug fidaxomicin.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

ARHGAP4-SEPT2-SEPT9 complex enables both up- and down-modulation of integrin-mediated focal adhesions, cell migration, and invasion

Na Kang et al.

Summary: The study demonstrates that the Rho-GTPase-activating protein ARHGAP4 forms a complex with SEPT2 and SEPT9, which regulates cell migration and invasion capabilities, and affects the reorganization of focal adhesions.

MOLECULAR BIOLOGY OF THE CELL (2021)

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Article Gastroenterology & Hepatology

DNA Damage-Regulated Autophagy Modulator 1 (DRAM1) Mediates Autophagy and Apoptosis of Intestinal Epithelial Cells in Inflammatory Bowel Disease

Yu Zhang et al.

Summary: DRAM1 expression is associated with the pathogenesis of inflammatory bowel disease, potentially affecting the processes of autophagy and apoptosis. Inhibition of DRAM1 can alleviate colitis symptoms, and its regulation may involve positively regulating JNK activation to impact autophagy and apoptosis.

DIGESTIVE DISEASES AND SCIENCES (2021)

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Article Biotechnology & Applied Microbiology