Publications
Extramacrochaetae regulates Notch signaling in the Drosophila eye through non-apoptotic caspase activity
Description: Many cell fate decisions are determined transcriptionally. Accordingly, some fate specification is prevented by Inhibitor of DNA binding (Id) proteins that interfere with DNA binding by master regulatory transcription factors. We show that the Drosophila Id protein Extra macrochaetae (Emc) also affect developmental decisions by regulating caspase activity. Emc, which prevents proneural bHLH transcription factors from specifying neural cell fate, also prevents homodimerization of another bHLH.
Published: Monday, August 12, 2024
VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma
Description: CONCLUSIONS: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA-VSIG axis to enhance anti-tumor responses.
Published: Saturday, August 10, 2024
The Id protein Extramacrochaetae restrains the E protein Daughterless to regulate Notch, Rap1, and Sevenless within the R7 equivalence group of the Drosophila eye
Description: The Drosophila Id gene extramacrochaetae (emc) is required during Drosophila eye development for proper cell fate specification within the R7 equivalence group. Without emc, R7 cells develop like R1/6 cells, and there are delays and deficits in differentiation of non-neuronal cone cells. Although emc encodes an Inhibitor of DNA-binding (Id) protein that is known to antagonize proneural bHLH protein function, no proneural gene is known for R7 or cone cell fates. These fates are also independent...
Published: Tuesday, July 23, 2024
Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?
Description: Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a...
Published: Thursday, July 4, 2024
Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy
Description: Chaperone-mediated autophagy (CMA) is part of the mammalian cellular proteostasis network that ensures protein quality control, maintenance of proteome homeostasis, and proteome changes required for the adaptation to stress. Loss of proteostasis is one of the hallmarks of aging. CMA decreases with age in multiple rodent tissues and human cell types. A decrease in lysosomal levels of the lysosome-associated membrane protein type 2A (LAMP2A), the CMA receptor, has been identified as a main reason...
Published: Tuesday, June 18, 2024
Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV
Description: People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm³ to immediate versus deferred ART. We previously...
Published: Thursday, May 2, 2024
Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome
Description: CONCLUSIONS: TPOm interacts with BM vascular and stromal niches to locally support hematopoietic reconstitution and systemically improve survival in mice after TBI. Therefore, this work warrants the development of TPOm as a potent radiation MCM for the treatment of ARS.
Published: Sunday, April 28, 2024
A zebrafish xenotransplant model of anaplastic thyroid cancer to study tumor microenvironment and innate immune cell interactions in vivo
Description: Anaplastic thyroid cancer (ATC) is of the most aggressive thyroid cancer. While ATC is rare, it accounts for a disproportionately high number of thyroid cancer-related deaths. Here, we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643)-derived fluorescently labeled ATC cell lines, we show these cell lines display different engraftment rates, mass volume, proliferation, cell...
Published: Wednesday, April 24, 2024
Transcription factor Nrf1 regulates proteotoxic stress-induced autophagy
Description: Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding to proteotoxic stress elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates new proteasome synthesis, thus enabling the cells to mitigate the proteotoxic stress. Here, we report that under similar circumstances,...
Published: Wednesday, April 24, 2024
Next questions in autophagy
Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the study of muscle, mobility and aging (SOMMA)
Description: Autophagy is essential for proteostasis, energetic balance, and cell defense and is a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study of Muscle, Mobility, and Aging (SOMMA). For 575 participants, RNA was sequenced and expression of 281 genes related to...
Published: Wednesday, April 17, 2024
2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation
Description: In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for...
Published: Friday, April 12, 2024
2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation
Description: In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for...
Published: Wednesday, April 10, 2024
2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation
Description: In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for...
Published: Monday, April 8, 2024
Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway
Description: Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution, a process characterized by reduction of BAT mass and function with increased lipid droplet size. Single nuclei RNA sequencing of aged mice identifies a specific brown adipocyte population of Ucp1-low cells that are pyroptotic and display a reduction in the longevity gene syntaxin 4 (Stx4a). Similar to aged brown adipocytes, Ucp1-STX4KO mice display loss of brown adipose tissue mass...
Published: Tuesday, April 2, 2024
Human Adenovirus B3 Associated Colitis and Hemophagocytic Lymphohistiocytosis in 9-Year-old Previously Healthy Girl
The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis
Description: Canonical Wnt and sphingosine-1-phosphate (S1P) signaling pathways are highly conserved systems that contribute to normal vertebrate development, with key consequences for immune, nervous, and cardiovascular system function; despite these functional overlaps, little is known about Wnt/β-catenin-S1P cross-talk. In the vascular system, both Wnt/β-catenin and S1P signals affect vessel maturation, stability, and barrier function, but information regarding their potential coordination is scant. We...
Published: Wednesday, March 13, 2024
Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome
Description: CONCLUSIONS: TPOm interacts with BM vascular and stromal niches to locally support hematopoietic reconstitution and systemically improve survival in mice after TBI. Therefore, this work warrants the development of TPOm as a potent radiation MCM for the treatment of ARS.
Published: Monday, March 11, 2024
International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis
Description: Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or...
Published: Tuesday, March 5, 2024
Improving Unrelated Donor Equity: Assessing Mismatched Donor Opportunities with Real-World Data in a Minority-Predominant Cohort
Description: Recent advances in graft-versus-host disease (GVHD) prophylaxis including post-transplant cyclophosphamide (PTCy) and abatacept have significantly improved outcomes following HLA-mismatched allogenic hematopoietic stem cell transplantation (allo-HSCT) and have tremendous potential for reducing racial disparities in donor availability. A recent small study employing bone marrow as the source of stem cells showed similar outcomes after 5/8 versus 7/8 matches and is currently being tested in a...
Published: Wednesday, February 28, 2024
Inflammation in Development and Aging: Insights from the Zebrafish Model
Description: Zebrafish are an emergent animal model to study human diseases due to their significant genetic similarity to humans, swift development, and genetic manipulability. Their utility extends to the exploration of the involvement of inflammation in host defense, immune responses, and tissue regeneration. Additionally, the zebrafish model system facilitates prompt screening of chemical compounds that affect inflammation. This study explored the diverse roles of inflammatory pathways in zebrafish...
Published: Saturday, February 24, 2024
Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability
Description: Nascent proteins destined for the cell membrane and the secretory pathway are targeted to the endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing the protein TMEM208, is one of three pathways that facilitates the translocation of nascent proteins into the ER. The in vivo function of this protein is ill characterized in multicellular organisms. Here, we generated a CRISPR-induced null allele of the fruit fly ortholog...
Published: Wednesday, February 21, 2024
Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency
Description: While therapies targeting CD19 by antibodies, chimeric antigen receptor T cells (CAR-T), and T cell engagers have improved the response rates in B cell malignancies, the emergence of resistant cell populations with low CD19 expression can lead to relapsed disease. We developed an in vitro model of adaptive resistance facilitated by chronic exposure of leukemia cells to a CD19 immunotoxin. Single-cell RNA-Seq (scRNA-Seq) showed an increase in transcriptionally distinct CD19lo populations among...
Published: Tuesday, February 20, 2024
Broad de-regulated U2AF1 splicing is prognostic and augments leukemic transformation via protein arginine methyltransferase activation
Description: The role of splicing dysregulation in cancer is underscored by splicing factor mutations; however, its impact in the absence of such rare mutations is poorly understood. To reveal complex patient subtypes and putative regulators of pathogenic splicing in Acute Myeloid Leukemia (AML), we developed a new approach called OncoSplice. Among diverse new subtypes, OncoSplice identified a biphasic poor prognosis signature that partially phenocopies U2AF1-mutant splicing, impacting thousands of genes in...
Published: Monday, February 19, 2024
RNA helicase DDX3 regulates RAD51 localization and DNA damage repair in Ewing sarcoma
Description: We previously demonstrated that RNA helicase DDX3X (DDX3) can be a therapeutic target in Ewing sarcoma (EWS), but its role in EWS biology remains unclear. The present work demonstrates that DDX3 plays a unique role in DNA damage repair (DDR). We show that DDX3 interacts with several proteins involved in homologous recombination, including RAD51, RECQL1, RPA32, and XRCC2. In particular, DDX3 colocalizes with RAD51 and RNA:DNA hybrid structures in the cytoplasm of EWS cells. Inhibition of DDX3 RNA...
Published: Wednesday, February 7, 2024
Treatment decision for recurrences in non-small cell lung cancer during or after adjuvant osimertinib: an international Delphi consensus report
Description: INTRODUCTION: Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in...
Published: Wednesday, February 7, 2024
Cell surface RNAs control neutrophil recruitment
Description: RNAs localizing to the outer cell surface have been recently identified in mammalian cells, including RNAs with glycan modifications known as glycoRNAs. However, the functional significance of cell surface RNAs and their production are poorly known. We report that cell surface RNAs are critical for neutrophil recruitment and that the mammalian homologs of the sid-1 RNA transporter are required for glycoRNA expression. Cell surface RNAs can be readily detected in murine neutrophils, the...
Published: Tuesday, January 23, 2024
Signaling events at TMEM doorways provide potential targets for inhibiting breast cancer dissemination
Description: Tumor cell intravasation is essential for metastatic dissemination, but its exact mechanism is incompletely understood. We have previously shown that in breast cancer, the direct and stable association of a tumor cell expressing Mena, a Tie2^(hi)/VEGF^(hi) macrophage, and a vascular endothelial cell, creates an intravasation portal, called a "tumor microenvironment of metastasis" (TMEM) doorway, for tumor cell intravasation, leading to dissemination to distant sites. The density of TMEM...
Published: Tuesday, January 23, 2024
Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice
Description: Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in...
Published: Thursday, December 28, 2023
Nucleic acid-induced inflammation on hematopoietic stem cells
Description: Hematopoiesis, the process of generating blood cells, starts during development with the primitive, pro-definitive, and definitive hematopoietic waves. The first two waves will generate erythrocytes and myeloid cells, although the definitive wave will give rise to hematopoietic stem cells (HSCs) that are multipotent and can produce most of the blood cells in an adult. Although HSCs are highly proliferative during development, during adulthood they remain quiescent in the bone marrow....
Published: Wednesday, December 27, 2023
Molecular determinants of the crosstalk between endosomal microautophagy and chaperone-mediated autophagy
Description: Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively. These autophagic processes share as a first step the recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 chaperone, raising the possibility of coordinated activity of both pathways. In this work, we show the existence of a compensatory relationship between CMA and eMI and identify a role for...
Published: Thursday, December 7, 2023
NGLY1 mutations cause protein aggregation in human neurons
Description: Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1's activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons....
Published: Friday, December 1, 2023
Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the Study of Muscle, Mobility and Aging (SOMMA)
Description: Autophagy is an essential component of proteostasis and a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study of Muscle, Mobility and Aging (SOMMA). For 575 participants, RNA was sequenced and expression of 281 genes related to autophagy regulation, mitophagy...
Published: Tuesday, November 14, 2023
Ups and downs of lysosomal pH: conflicting roles of LAMP proteins?
Description: The acidic pH of lysosomes is critical for catabolism in eukaryotic cells and is altered in neurodegenerative disease including Alzheimer and Parkinson. Recent reports using Drosophila and mammalian cell culture systems have identified novel and, at first sight, conflicting roles for the lysosomal associated membrane proteins (LAMPs) in the regulation of the endolysosomal system.Abbreviation: AD: Alzheimer disease; LAMP: lysosomal associated membrane protein; LTR: LysoTracker; PD: Parkinson...
Published: Tuesday, November 14, 2023
Impact of race and ethnicity on early mortality in multiple myeloma: a SEER analysis
Description: Over the past two decades, there have been significant advances in the treatment of multiple myeloma which has led to an improvement in overall survival.1,2 However, a notable proportion of patients continue to experience early mortality (EM), defined as 2 years from the time of diagnosis. This raises the possibility that improvements in myeloma survival have not extended equally to all groups. Using the latest data drawn from the Surveillance Epidemiology and End Results database of patients in...
Published: Thursday, October 26, 2023
Delayed Solid Tumor Presentations in Adolescent and Young Adults Patients in the Bronx
Description: Adolescent and young adults (AYAs) require support from their parents and caregivers. While there are formal programs available for patients with complex medical problems, 20% of pediatric practices are performing transition readiness processes in patients aged 12-17 years to effective transition. Although cancer is the most common cause of disease-related death in AYAs in high-income countries, AYA oncology patients have not attained the same clinical improvements as pediatric patients, and...
Published: Monday, October 23, 2023
Protocol for assessing translation in living Drosophila imaginal discs by O-propargyl-puromycin incorporation
Description: Translation is a fundamental process of cellular behavior. Here, we present a protocol for measuring translation in Drosophila epithelial tissues using O-propargyl-puromycin (OPP), a puromycin derivative. We detail steps for larval dissection, OPP incorporation, fixation, OPP labeling, immunostaining, and imaging. We also provide details of quantification analysis. Significantly, OPP addition to methionine-containing media enables polypeptide labeling in living cells. Here, we study wing...
Published: Friday, October 20, 2023
A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion
Description: Intracellular degradation of proteins and organelles by the autophagy-lysosome system is essential for cellular quality control and energy homeostasis. Besides degradation, endolysosomal organelles can fuse with the plasma membrane and contribute to unconventional secretion. Here, we identify a function for mammalian SKP1 in endolysosomes that is independent of its established role as an essential component of the family of SCF/CRL1 ubiquitin ligases. We found that, under nutrient-poor...
Published: Friday, October 13, 2023
Unanticipated domain requirements for Drosophila Wnk kinase in vivo
Description: WNK (With no Lysine [K]) kinases have critical roles in the maintenance of ion homeostasis and the regulation of cell volume. Their overactivation leads to pseudohypoaldosteronism type II (Gordon syndrome) characterized by hyperkalemia and high blood pressure. More recently, WNK family members have been shown to be required for the development of the nervous system in mice, zebrafish, and flies, and the cardiovascular system of mice and fish. Furthermore, human WNK2 and Drosophila Wnk modulate...
Published: Wednesday, October 11, 2023
Phosphoproteome analysis of the crosstalk between sumoylation and phosphorylation in mouse spermatocytes
Description: Spermatogenesis is supported by various posttranslational modifications. There is growing evidence supporting a crosstalk between sumoylation and phosphorylation in different cell types. We have recently shown that inhibition of global sumoylation with a sumoylation inhibitor (Ginkgolic acid, GA) arrested purified mouse spermatocytes in vitro; the spermatocytes could not condense chromatin and disassemble the synaptonemal complex. Our data have also revealed that some kinases regulating the...
Published: Monday, October 2, 2023
Complement C3 Reduces Apoptosis via Interaction with the Intrinsic Apoptotic Pathway
Description: Myocardial ischemia/reperfusion (I/R) elicits an acute inflammatory response involving complement factors. Recently, we reported that myocardial necrosis was decreased in complement C3^(-/-) mice after heart I/R. The current study used the same heart model to test the effect of C3 on myocardial apoptosis and investigated if C3 regulation of apoptosis occurred in human cardiomyocytes. Comparative proteomics analyses found that cytochrome c was present in the myocardial C3 complex of WT mice...
Published: Thursday, September 28, 2023
Interplay between diet, circulating indolepropionate concentrations and cardiometabolic health in US populations
Description: CONCLUSIONS: Specific microbial species and dietary fibre jointly predicted significantly higher circulating IPA concentrations at higher tryptophan intake. Dietary and plasma tryptophan, as well as its kynurenine pathway metabolites, demonstrated divergent associations from those for IPA, which was significantly predictive of lower risk of T2D.
Published: Friday, September 22, 2023
Primary central nervous system lymphoma: treatment access and outcomes in HIV positive patients in a minority rich cohort
Ferroptosis in cancer immunity and immunotherapy: Multifaceted interplay and clinical implications
Description: Ferroptosis is a type of cell death characterized by iron-dependent phospholipid peroxidation and reactive oxygen species overproduction. Ferroptosis induces immunogenic cell death and elicits anti-tumor immune responses, playing an important role in cancer immunotherapy. Ferroptosis suppression in cancer cells impairs its immunotherapeutic efficacy. To overcome this issue, ferroptosis inducers (FINs) have been combined with other cancer therapies to create an anti-tumor immune microenvironment....
Published: Friday, September 1, 2023
Next-generation sequencing of baseline genetic mutations and outcomes of eltrombopag and azacitidine therapy in patients with myelodysplastic syndromes and thrombocytopenia: Data from the SUPPORT clinical trial
Description: Eltrombopag has been previously shown to be effective in reversing azacitidine-mediated thrombocytopenia. This was further investigated in the SUPPORT trial, a phase III study assessing the efficacy/safety of eltrombopag plus azacitidine in patients with intermediate- to high-risk myelodysplastic syndromes and thrombocytopenia. The results did not support a clinical benefit for the addition of eltrombopag to azacitidine. We investigated if the somatic mutational profiles in the patient cohort...
Published: Monday, August 21, 2023
Association of HIV and viral suppression status with hospital acute kidney injury in the era of antiretroviral therapy
Description: In the modern era, it is unknown if people that are virally suppressed with HIV (PWH) are at increased risk for acute kidney injury (AKI) compared to people without HIV and no studies have compared the risk of AKI by viral suppression status. Here, we determined the associations of HIV status and AKI among PWH with and without viral suppression compared to people without HIV. An observational cohort study of PWH and people without HIV hospitalized in a large New York City health system between...
Published: Sunday, August 20, 2023
Drivers of Differential Time to Diagnosis in Pediatric ALL Tied to Race and Ethnicity
Description: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with diagnosis preceded by symptoms that may include fever, weight loss, fatigue, bleeding, and bruising. Timely diagnosis and treatment of ALL may lead to improved outcomes and reduced morbidity from associated complications, including tumor lysis syndrome, hyperviscosity, and stroke. We performed a retrospective cohort analysis of 274 pediatric pre-B cell ALL and acute lymphoblastic lymphoma patients within Montefiore...
Published: Tuesday, August 1, 2023
Role of IL8 in myeloid malignancies
Description: Aberrant overexpression of Interleukin-8 (IL8) has been reported in Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPNs) and other myeloid malignancies. IL8 (CXCL8) is a CXC chemokine that is secreted by aberrant hematopoietic stem and progenitors as well as other cells in the tumor microenvironment. IL8 can bind to CXCR1/CXCR2 receptors and activate oncogenic signaling pathways, and also increase the recruitment of myeloid derived suppressor cells...
Published: Wednesday, July 19, 2023
SF3B1 mutation and ATM deletion codrive leukemogenesis via centromeric R-loop dysregulation
Description: RNA splicing factor SF3B1 is recurrently mutated in various cancers, particularly in hematologic malignancies. We previously reported that coexpression of Sf3b1 mutation and Atm deletion in B cells, but not either lesion alone, leads to the onset of chronic lymphocytic leukemia (CLL) with CLL cells harboring chromosome amplification. However, the exact role of Sf3b1 mutation and Atm deletion in chromosomal instability (CIN) remains unclear. Here, we demonstrated that SF3B1 mutation promotes...
Published: Tuesday, July 18, 2023