Translation defects in ribosomopathies
Purpose of review
Congenital or acquired ribosomopathies related to mutations or deletions in ribosomal proteins gene or ribosome-associated proteins exhibit defective ribosome biogenesis that expose the cell to translation defects. The mechanisms leading to low translation rate, loss-of-translation fidelity and translation selectivity are reviewed.
Recent findings
New quantitative techniques to measure ribosome component stoichiometry reveal that the pool of ribosomes could be heterogeneous and/or decreased with a limited number of translationally competent ribosomes. During development or cell differentiation,...
Source: Current Opinion in Hematology - April 28, 2022 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
PIEZO1, sensing the touch during erythropoiesis
Purpose of review
Awarding the 2021 Nobel to Ardem Patapoutian for the discovery of the PIEZO mechanotransducers has emphasized the importance of touch-sensing mechanisms in cell physiology. It is well known that PIEZO1 is expressed at the surface of red blood cells where it adjusts their hydration status under mechanical constraints. Besides this, recent findings suggest that PIEZO1 plays a broader role in erythroid lineage. This review aims to actualize the knowledge on PIEZO1 functions all along erythropoiesis.
Recent findings
PIEZO1 is expressed in erythroid progenitors, and controls proliferation and differ...
Source: Current Opinion in Hematology - April 28, 2022 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
Translational control by heme-regulated elF2α kinase during erythropoiesis
Purpose of review
HRI is the heme-regulated elF2α kinase that phosphorylates the α-subunit of elF2. Although the role of HRI in inhibiting globin synthesis in erythroid cells is well established, broader roles of HRI in translation have been uncovered recently. This review is to summarize the new discoveries of HRI in stress erythropoiesis and in fetal γ-globin expression.
Recent findings
HRI and activating transcription factor 4 (ATF4) mRNAs are highly expressed in early erythroblasts. Inhibition of protein synthesis by HRI-phosphorylated elF2α (elF2αP) is necessary to maintain protein homeostasis in both ...
Source: Current Opinion in Hematology - April 28, 2022 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 28, 2022 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
The significance of CUX1 and chromosome 7 in myeloid malignancies
Purpose of review
Loss of chromosome 7 has long been associated with adverse-risk myeloid malignancy. In the last decade, CUX1 has been identified as a critical tumor suppressor gene (TSG) located within a commonly deleted segment of chromosome arm 7q. Additional genes encoded on 7q have also been identified as bona fide myeloid tumor suppressors, further implicating chromosome 7 deletions in disease pathogenesis. This review will discuss the clinical implications of del(7q) and CUX1 mutations, both in disease and clonal hematopoiesis, and synthesize recent literature on CUX1 and other chromosome 7 TSGs.
Recent find...
Source: Current Opinion in Hematology - February 2, 2022 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene Source Type: research
Azacitidine maintenance in AML post induction and posttransplant
Purpose of review
Disease relapse remains the most common cause of death among patients with acute myeloid leukemia (AML) following induction therapy and allogeneic hematopoietic cell transplant (allo-HCT). Prolonging the duration of remission with minimal nonrelapse mortality risk is an area of unmet need for AML patients.
Recent findings
In QUAZAR AML-001 study, the oral azacitidine analogue CC-486 demonstrated an overall survival (OS) benefit when given as postremission therapy (PRT) for patients in CR1 that were ineligible to proceed to allo-HCT. Used as maintenance post allo-HCT, CC-486 has also shown safet...
Source: Current Opinion in Hematology - February 2, 2022 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene Source Type: research
Chimeric antigen receptor T-cell therapy in acute myeloid leukemia
Purpose of review
Treatment outcome of relapsed or refractory AML patients remains dismal and new treatment options are needed. Adoptive cell therapy using CAR-T cells is a potentially interesting approach in this.
Recent findings
Several potentially interesting AML targets are being investigated with CAR-T therapy with over 60 clinical trials listed on clinicaltrials.gov. The first clinical data are only just emerging with mixed results, once more proving that further research is needed.
Summary
Adoptive cell therapy using chimeric antigen receptor T cells is being investigated in AML through many clinic...
Source: Current Opinion in Hematology - February 2, 2022 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene Source Type: research
Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes
Purpose of review
Venetoclax is a BCL-2 inhibitor that was approved in combination therapy with hypomethylating agents or low dose cytarabine for newly diagnosed acute myeloid leukemia (AML). The purpose of this review is to outline the most recent venetoclax-based combination therapies in newly diagnosed or relapsed myelodysplastic syndrome (MDS) and AML patients.
Recent finding
Venetoclax has been incorporated in various therapeutic regimens – either with chemotherapy, immunotherapy or targeted therapies. These combinations achieve high remission rates with deep molecular responses, as suggested by measurabl...
Source: Current Opinion in Hematology - February 2, 2022 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - February 2, 2022 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research
Casting a NET on cancer: the multiple roles for neutrophil extracellular traps in cancer
Purpose of review
The role of the innate immune system has become widely appreciated in cancer and cancer-associated disorders. Neutrophils, the most abundant circulating leukocytes, have prognostic value in determining cancer progression and survival. One of the ways by which neutrophils negatively impact outcome is by formation of neutrophil extracellular traps (NETs) which result in release of nuclear chromatin and bioactive proteins into the extracellular space. Here, we review the evidence for NETs contributions to cancer progression, metastasis, and cancer-associated thrombosis (CAT).
Recent findings
NETs ...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
Targeting the cluster of differentiation 47/signal-regulatory protein alpha axis in myeloid malignancies
Purpose of review
The antitumor activity of macrophages is regulated by a balance of prophagocytic and antiphagocytic signals. Cluster of differentiation 47 (CD47), the dominant macrophage immune checkpoint (‘do not eat me’ signal), interacts with its receptor signal-regulatory protein alpha (SIRPα) to suppress phagocytic activities. This axis plays a pivotal role in immune evasion in myeloid malignancies as well as multiple cancers providing strong rationale for therapeutic exploitation.
Recent findings
Preclinical studies have revealed overexpression of CD47 on leukemic stem cells and myeloblasts from pat...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance
Purpose of review
Advancements in the next-generation sequencing technologies have identified rare transcripts of long noncoding RNAs (lncRNAs) in the genome of cancers, including in acute myeloid leukemia (AML). The purpose of this review is to highlight the contribution of lncRNAs in AML pathogenesis, prognosis, and chemoresistance.
Recent findings
Several studies have recently reported that deregulated lncRNAs are novel key players in the development of AML and are associated with AML pathophysiology and may serve as prognostic indicators. A few aberrantly expressed lncRNAs that correlated with the recurrent ...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
Congenital neutropenia: disease models guiding new treatment strategies
Purpose of review
Myeloid diseases are often characterized by a disturbed regulation of myeloid cell proliferation, survival, and maturation. This may either result in a severe paucity of functional neutrophils (neutropenia), an excess production of mature cells (myeloproliferative disorders) or in clonal expansions of dysplastic or immature myeloid cells (myelodysplasia and acute myeloid leukemia). Although these conditions can be regarded as separate entities, caused by the accumulation of distinct sets of somatic gene mutations, it becomes increasingly clear that they may also evolve as the prime consequence of a co...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
Abnormal monocyte differentiation and function in chronic myelomonocytic leukemia
Purpose of review
Monocytes serve as the phagocytic defense surveillance system of the human body. Although there is comprehensive evidence regarding monocyte development, characterization and function under steady state hematopoietic continuum, the deviations and complexities in the monocyte secretome during myeloid malignancies have not been comprehensively examined and delineated.
Recent findings
This review summarizes the aspects of development, functions, transcriptional and cytokine-mediated regulation of monocytes during steady state hematopoiesis and also contrasts the aberrations observed in myelomonocy...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies
Purpose of review
Cell intrinsic and extrinsic perturbations to inflammatory signaling pathways are a hallmark of development and progression of hematologic malignancies. The interleukin 1 receptor-associated kinases (IRAKs) are a family of related signaling intermediates (IRAK1, IRAK2, IRAK3, IRAK4) that operate at the nexus of multiple inflammatory pathways implicated in the hematologic malignancies. In this review, we explicate the oncogenic role of these kinases and review recent therapeutic advances in the dawning era of IRAK-targeted therapy.
Recent findings
Emerging evidence places IRAK signaling at the c...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
