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MSI2 protective variant against blood cancer discovered

MSI2 protective variant against blood cancer discovered

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By Newzino Staff | |

Multi-institutional study identifies genetic change that suppresses precancerous blood cell expansion

January 24th, 2026: Research Gains Widespread Attention

Overview

For decades, cancer genetics meant finding mutations that raise risk. Now scientists have found one that lowers it. A variant in the MSI2 gene reduces the risk of blood cancers by up to 30% in people who carry two copies—the first protective genetic variant identified against myeloid malignancies.

The discovery, published January 1, 2026 in Science by researchers from Memorial Sloan Kettering, Harvard, and Vanderbilt, opens a new therapeutic frontier. Rather than just identifying who's at risk, the finding points toward interventions that could prevent blood cancer by mimicking what this natural variant does: dial down a protein that precancerous cells need to outcompete healthy ones.

Key Indicators

30%
Risk reduction (two copies)
People with the variant in both gene copies show 30% decreased risk of clonal hematopoiesis
20%
Myeloid disease protection
Single-copy carriers have 20% lower risk of developing myeloid malignancies including leukemia
4%
Global variant prevalence
Approximately 4% of humans carry this protective variant, with highest rates in Finnish populations
1.8x
Clone regression likelihood
Variant carriers are 1.8 times more likely to see precancerous blood cell clones disappear entirely

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People Involved

Michael Kharas
Michael Kharas
Cancer biologist, Memorial Sloan Kettering Cancer Center (Co-corresponding author of the Science paper)
Vijay Sankaran
Vijay Sankaran
Physician-scientist, Harvard Stem Cell Institute and Boston Children's Hospital (Senior author of the Science paper)
Alexander Bick
Alexander Bick
Director, Division of Genetic Medicine, Vanderbilt University Medical Center (Co-author leading validation studies)
Yash Pershad
Yash Pershad
MD/PhD student, Bick Lab at Vanderbilt (Led longitudinal validation analysis)
Koichi Takahashi
Koichi Takahashi
Oncologist and cancer researcher, MD Anderson Cancer Center (Expert commentator on therapeutic implications)

Organizations Involved

Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
Cancer Research Hospital
Status: Co-led the research

One of the world's premier cancer centers, where the Kharas lab has studied MSI2 for over a decade.

Harvard Stem Cell Institute
Harvard Stem Cell Institute
Academic Research Institute
Status: Co-led the research

Harvard's hub for stem cell science, where Sankaran's lab studies genetic variation in blood cell production.

Vanderbilt BioVU
Vanderbilt BioVU
DNA Biobank
Status: Provided longitudinal validation data

The world's largest DNA biobank linked to electronic health records at a single academic center.

JAMA Oncology
JAMA Oncology
Medical Journal
Status: Published related CHIP-cardiovascular research

Peer-reviewed oncology journal that published complementary research on clonal hematopoiesis and cardiovascular disease risk.

Timeline

  1. Research Gains Widespread Attention

    Coverage

    Multiple outlets report on the MSI2 discovery, highlighting implications for blood cancer prevention and potential therapeutic development.

  2. CHIP Linked to Heart Disease Risk After Cancer Treatment

    Research

    Bick lab published in JAMA Oncology showing that 1 in 5 cancer patients with clonal hematopoiesis face increased cardiovascular disease risk following cancer therapy, supporting the need for CHIP screening before treatment.

  3. Protective MSI2 Variant Discovery Published

    Publication

    Science published the multi-institutional study identifying rs17834140-T variant that reduces blood cancer risk by up to 30%, with mechanism explained.

  4. FDA Approves First Gene Therapy for Sickle Cell

    Regulatory

    Casgevy approved by FDA, based partly on Sankaran's research on BCL11A—demonstrating his lab's track record translating genetic discoveries to therapies.

  5. TCL1A Identified as Blood Cancer Prevention Target

    Research

    Bick lab published in Nature identifying TCL1A as a gene driving clonal expansion, suggesting drugs targeting it could suppress cancerous growth.

  6. First MSI2 Inhibitor Molecule Identified

    Drug Development

    Kharas lab reported in Nature Communications that compound 'Ro' blocks Musashi-2 function, eliminating tumor cells and normalizing leukemic cells in mice.

  7. MSI2 Role in Myeloid Leukemia Confirmed

    Research

    Nature Genetics published functional screen identifying MSI2's essential role in myeloid leukemia stem cells through its interaction with SYNCRIP.

  8. Kharas Lab Links MSI2 to Leukemia Stem Cells

    Research

    Published in Journal of Clinical Investigation, demonstrating that Musashi2 sustains the stem cell program in MLL-driven leukemia.

  9. Landmark NEJM Studies on Clonal Hematopoiesis

    Publication

    New England Journal of Medicine published studies showing clonal hematopoiesis is a strong risk factor for blood cancer (12.9x hazard ratio) and associated with increased mortality.

  10. TET2 Mutations Linked to Clonal Hematopoiesis

    Research

    Nature Genetics published research identifying recurrent somatic TET2 mutations in elderly individuals with clonal hematopoiesis, establishing the genetic basis of CHIP.

  11. Musashi Gene Discovered in Fruit Flies

    Discovery

    Neurobiologist Craig Montell identified the Musashi gene controlling cell division in Drosophila. Named for the Japanese samurai's two swords, referencing the double-bristle mutation phenotype.

Scenarios

1

MSI2 Inhibitor Enters Clinical Trials Within 5 Years

Discussed by: Memorial Sloan Kettering researchers, given their 2019 proof-of-concept with compound Ro

Building on the Kharas lab's existing MSI2 inhibitor work, pharmaceutical partners develop a drug that mimics the protective variant's effect by reducing MUSASHI2 protein levels. Clinical trials target high-risk CHIP patients—those with 60% cancer progression risk over 5-10 years. Success would establish blood cancer prevention as a new therapeutic category.

2

Gene Therapy Approach Developed to Edit MSI2 Region

Discussed by: Harvard Stem Cell Institute team, given Sankaran's track record with Casgevy

Following the CRISPR gene therapy model that produced Casgevy for sickle cell, researchers develop a gene editing approach to introduce the protective variant or mimic its effects in blood stem cells. This would be more invasive than drug therapy but potentially offer permanent protection for highest-risk individuals.

3

Genetic Testing for MSI2 Variant Becomes Standard CHIP Screening

Discussed by: Vanderbilt researchers and clinical geneticists studying CHIP management

As clonal hematopoiesis screening expands, testing for the MSI2 protective variant becomes routine. Carriers can be reassured about lower progression risk; non-carriers with CHIP receive more intensive monitoring. This stratification improves resource allocation without requiring new drugs.

4

Population Ancestry Disparities Complicate Therapeutic Access

Discussed by: Bioethicists and health equity researchers noting the variant's uneven distribution

The protective variant is most common in Finnish populations and least common in Middle Eastern and East Asian populations. If MSI2-targeting therapies are developed, they may primarily benefit populations that already have natural protection, potentially widening health disparities unless explicitly addressed in clinical development.

Historical Context

CCR5-Δ32 and HIV Resistance (1996)

1996-2024

What Happened

Scientists discovered that a 32-base-pair deletion in the CCR5 gene renders homozygous carriers nearly immune to HIV infection. About 1% of Northern Europeans carry two copies. The discovery emerged from studying why some highly-exposed individuals never contracted HIV.

Outcome

Short Term

Identified CCR5 as HIV entry co-receptor, explaining the protective mechanism. Began hunt for drugs mimicking the deletion's effect.

Long Term

CCR5-targeted drugs (maraviroc) approved. At least five HIV patients 'cured' via stem cell transplants from CCR5-Δ32 donors. Gene therapy trials underway to edit CCR5 in patients' cells.

Why It's Relevant Today

The MSI2 discovery follows the same paradigm: natural protective variants pointing toward therapeutic targets. Like CCR5, MSI2 shows that studying why some people don't get sick can be as valuable as studying why others do.

BCL11A and Fetal Hemoglobin Reactivation (2008-2023)

December 2023

What Happened

Vijay Sankaran, co-author on the MSI2 paper, identified BCL11A as the switch suppressing fetal hemoglobin production in adults. People with naturally lower BCL11A activity had milder sickle cell disease. His lab developed gene therapy approaches to reduce BCL11A.

Outcome

Short Term

Proved that mimicking natural protective genetic variation could treat blood disorders.

Long Term

Casgevy, the first FDA-approved CRISPR gene therapy, uses BCL11A editing to treat sickle cell disease and beta-thalassemia. Over 45 patients treated in trials showed durable responses.

Why It's Relevant Today

Same research team, same approach: find people protected by natural variation, understand the mechanism, develop therapy that mimics it. MSI2 is their next target.

Tamoxifen and BRCA Carriers (1998-Present)

1998-Present

What Happened

While BRCA mutations dramatically increase breast cancer risk, researchers found that tamoxifen reduces contralateral breast cancer risk by 50-69% in BRCA carriers. This demonstrated that high-risk genetic status doesn't preclude effective prevention.

Outcome

Short Term

Established cancer prevention as viable strategy even in genetically high-risk populations.

Long Term

Chemoprevention became standard discussion for BRCA carriers. Showed that genetic risk assessment plus intervention beats genetic risk assessment alone.

Why It's Relevant Today

MSI2 research inverts this: instead of finding drugs for high-risk variants, it finds therapeutic targets from protective variants. But the goal is the same—using genetics to prevent cancer before it starts.

15 Sources:
+9
Memorial Sloan Kettering Cancer Center STAT News Vanderbilt University Medical Center News Harvard Stem Cell Institute Vanderbilt University Medical Center New England Journal of Medicine Journal of Clinical Investigation Proceedings of the National Academy of Sciences JAMA Oncology Medical Xpress GEN - Genetic Engineering & Biotechnology News EurekAlert! Sloan Kettering Institute Memorial Sloan Kettering Cancer Center Vanderbilt University Medical Center News