DocWire News Editors

DocwireNews

New research shows that high mobility group A1/2 (HMGA1/2) genes are overexpressed in MPN with highest levels in more advanced diseases such as myelofibrosis (MF), and acute myeloid leukemia (AML). The findings were presented at the 12th International Congress on Myeloproliferative Neoplasms.&nbsp;In this study, researchers compared HMGA1/2 in JAK2V617F mutant AML cell lines from MPN patients (DAMI, SET-2), CD34+ cells from PV patients during chronic and transformation phases, and JAK2V617F mouse models of PV (transgenic JAK2V617F) and PVAML (transgenic JAK2V617F/MPLSV).They noted that in order elucidate HMGA1/2 function, they silenced HMGA1 or HMGA2 via short hairpin RNA in human MPN-AML cells and subsequently generated murine models of PV and PV-AML with heterozygous Hmga1 or Hmga2 deficiency. Moreover, the researchers compared RNA-Seq from MPN-AML cell lines after gene silencing to assess molecular mechanisms underlying HMGA.The results of the study showed that HMGA1/2 mRNA are up-regulated in all JAK2V617F-positive contexts, including primary human PV CD34+ cells and total bone marrow from JAK2V617F mouse models for PV compared to controls. Also, the researchers observed a marked up-regulation in HMGA1/2 in CD34+ cells from PV patients after transformation to MF or AML and in leukemic blasts from our PV-AML mouse model. The results further displayed that silencing HMGA1 or HMGA2 in human MPN-AML cell lines significantly halts proliferation, disrupts clonogenicity, and prevents leukemia development in mice.&ldquo;In JAK2V617F murine models, heterozygous deficiency of Hmga1 prevents MPN progression to MF and prolongs survival in a fulminant MPN-AML model,&rdquo; the research authors wrote.&nbsp; &ldquo;Moreover, RNA-Seq analyses indicates that HMGA amplifies transcriptional networks involved cell cycle progression, which can be targeted with epigenetic therapies.&rdquo;They also said that their findings &ldquo;further underscore the key role for HMGA as an epigenetic switch required for transformation in MPN and opens the door to novel therapeutic approaches to prevent disease progression.&rdquo;Resar L, et al. High Mobility Group A Chromatin Regulators: Key Epigenetic Switches and Therapeutic Targets Required for MPN Progression. Presented at the 12th International Congress on Myeloproliferative Neoplasms; October 24-25, 2019; New York, NY.

Sara Nunnery, MD, MSCI

Reclassifying HER2: What Oncologists Need to Know About HER2-Low and -Ultralow Breast Cancer

HER2 Breast Cancer

Jeffrey Perl, MD

Joel M. Topf, MD, FACP

Thoughts From the 2025 Lazarus Award Winner

NKF Spring Clinical Meetings 2025

Brandon Twyford

DESTINY-Breast09 Demonstrates First-Line Superiority of Enhertu Plus Pertuzumab in HER2-Positive Metastatic Breast Cancer

Latest News

High Mobility Group A Chromatin Regulators: Key Epigenetic Switches and Therapeutic Targets Required for MPN Progression

MPN Conference Coverage 2019

New research shows that high mobility group A1/2 (HMGA1/2) genes are overexpressed in MPN with highest levels in more advanced diseases such as myelofibrosis (MF), and acute ...

High Mobility Group A Chromatin Regulators: Key Epigenetic Switches and Therapeutic Targets Required

About Us

Editorial Policy

Advertising

Contact Us

eNewsletters

Contribute

Career Center

MashupMD

Blood Cancers Today

Cancer Nursing Today

GU Oncology Now

Urban Health Today

Bile Duct Cancer

Colorectal Cancer

Gastroesophageal Cancer

Gastric Cancer

GEP-NETs

GIST

Liver Cancer

Pancreatic Cancer

GI Oncology Now

Anemia

Deep Vein Thrombosis

Essential Thrombocythemia

Hemophilia

Immune Thrombocytopenic Purpura

Myelodysplastic Syndromes

Myelofibrosis

Myeloproliferative Neoplasms

Polycythemia Vera

Pulmonary Embolism

Sickle Cell Disease

Thrombocytopenia

Thrombophilia

Thrombosis

Thrombotic Thrombocytopenic Purpura

Venous Thromboembolism

von Willebrand Disease

Heme Today

Acute Kidney Injury

ADPKD

Anemia and Kidney Disease

Chronic Kidney Disease

COVID-19 and Kidney Disease

Diabetes and Hypertension

End-Stage Renal Disease

Gout

Hyperkalemia

IgAN

Kidney Transplantation

Metabolic Acidosis

Nephrology Times

HR Breast Cancer

Triple-Negative Breast Cancer

Genetics & Breast Cancer

Breast Cancers Today

Atherosclerotic Disease

Atrial Fibrillation

Heart Failure

Hypertension

Interventional Cardiology

Lipid Management

Practice Tips With Dr. Lichaa

Preventive Cardiology

Stroke

Cardiology

Breast Cancer

Gynecologic Cancer

Head and Neck Cancer

Skin Cancer

Oncology

Sleep

Urology

Diabetes

Ophthalmology

— Demodex Blepharitis

Neurology

Rheumatology

Gastroenterology

Pulmonology

Infectious Diseases

— HIV

Health and Wellness

Lupus

Future of Medicine

Orthopedics

Pharmacology

Career News

More

Conferences

CardioNerds

The Sleep Source With Dr. Morse

Rheumatology Rounds With Dr. Maheswaranathan

Partners

Expert Interviews

Subscribe