Hereditary Hematologic Malignancy Genetics Program

This program helps to identify and provide comprehensive, coordinated medical care for families that have a hereditary risk for blood cancers.

Explore the Hereditary Hematologic Malignancy Genetics Program

The Hereditary Hematologic Malignancy Genetics Program helps to identify and provide comprehensive, coordinated medical care for families who may be at increased risk for developing cancers of the blood due to genetic factors. Our program is under the direction of Timothy Graubert, MD, and Andrew Brunner, MD, who are both oncologists and researchers at Mass General Cancer Center, and our team includes specialists in both hematology-oncology and genetics.

What Does It Mean to Have a Hereditary Risk for Hematologic Malignancies (Blood Cancers)?

Hematologic malignancies are cancers that affect the blood, bone marrow, and lymph nodes. Types of hematologic malignancies include leukemia and myelodysplastic syndrome (MDS), among others. In some cases, an inherited gene mutation may cause a person to develop a hematologic (blood) cancer.

Through our program, patients and families who may be at increased risk for developing hematologic malignancies (blood cancers) due to genetic factors meet with a genetic counselor to review family and medical history and discuss options for genetic testing.

Genetic testing for hereditary blood cancers may help guide patients and their family members regarding their future cancer risks. For individuals who need a stem cell transplant genetic testing results may help identify optimal stem cell donors.

Those identified to be at an increased risk for a blood cancer based on genetic testing may choose to be seen in the clinic of Andrew Brunner, MD at the Mass General Cancer Center. Dr. Brunner specializes in the evaluation and management of a number of hereditary conditions that predispose to hematologic malignancy risk.

Should You Consider Genetic Counseling?

Our program may be appropriate for individuals with any of the following:

A personal history of a blood cancer and abnormal genetic testing on bone marrow (somatic testing) showing specific genetic mutations. Doctors routinely test for these mutations during diagnosis
A personal or family history of a known hereditary hematologic malignancy (blood cancer) predisposition syndrome
A personal or family history of a blood cancer with or without thrombocytopenia (low platelet count)
A personal or family history of longstanding blood count abnormalities of unknown cause

Hereditary Blood Cancer Diseases

The syndromes most commonly discussed with patients in our hereditary hematologic malignancy program include:

DDX41 gene associated familial acute myeloid leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia
RUNX1 gene associated familial platelet disorder with propensity for myeloid malignancies
GATA2 gene associated familial acute myeloid leukemia or myelodysplastic syndrome
CEBPA gene associated acute myeloid leukemia
Telomere length biology syndromes or other inherited bone marrow failure conditions

FAQs

View answers to FAQs about the Hereditary Leukemia and Myelodysplastic Syndrome Panel, by our program's team of physicians and genetic counselors.

Here's what you need to know about this genetic test:

Is leukemia or myelodysplastic syndrome hereditary?

Leukemia and myelodysplastic syndrome (MDS) are types of cancer found in blood and bone marrow. There is not a lot of research, but some data shows that about 10% of cases of leukemia and MDS are due to an inherited risk. There are certain genes that are associated with an increased risk for leukemia and MDS. Some of these genes are linked to hereditary cancer syndromes that increase the risk for other health issues as well. Families with many cases of leukemia, MDS, and/or bleeding and bruising disorders may have a higher chance to have an inherited cancer risk.

What genes are linked to hereditary leukemia or myelodysplastic syndrome?

Cancer genetics is an active area of research. People who inherit pathogenic variants (or mutations) in the genes below have an increased risk for leukemia and MDS. This is not a full list; more genes may be discovered in the future.

Gene	Cancer types*	Approximate lifetime risk	Other possible features
CEBPA	AML	100%	-
DDX41	MDS, AML, CML	20-30%	-
RUNX1	MDS, AML, ALL	35-40%	Thrombocytopenia, increased bleeding risk
ANKRD26	MDS, AML	Elevated	Thrombocytopenia, increased bleeding risk
ETV6	MDS, AML, ALL	30%	Thrombocytopenia, increased bleeding risk
GATA2	MDS, AML, Bone marrow failure	70%	Immune deficiency, sensorineural hearing loss, lymphedema, and other features
SRP72	MDS, Aplastic anemia	Unknown	Sensorineural hearing loss

*Acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL)

What does it mean to have a pathogenic variant in a gene linked to hereditary leukemia or myelodysplastic syndrome?

If you have a pathogenic variant in one of the genes listed above, this means you have a higher chance to develop leukemia and/or MDS compared to individuals in the general population. The lifetime risk for leukemia in the general population is estimated to be 1.6%.
If the test shows that you have a pathogenic variant in one of these genes, your doctors may recommend a specialized care plan to manage the increased cancer risks. In some cases, your results may also help to guide treatment options. There are currently no treatments to reduce the risk of developing leukemia or MDS in individuals with a pathogenic variant.
There is a 50% chance that a person with a pathogenic variant will pass it on to their children. In most cases, siblings also have a 50% chance to have the pathogenic variant. Other family members may also have the pathogenic variant.

What should I consider before genetic testing for hereditary leukemia and myelodysplastic syndrome?

Testing may not include all genes linked to an increased risk of all types of cancer or even all blood and bone marrow-related cancers.
Your test may find variants of uncertain significance (VUS). VUS are genetic changes which may or may not increase the risk for cancer. Most VUS turn out not to increase cancer risk.
The test may find a pathogenic variant in a gene with features that do not match with your family history.
The understanding of some of these genes are limited.
More genes may be discovered in the future.

Precursor Blood Conditions

Some blood cancers may be preceded by precursor conditions, which can sometimes be identified during routine blood tests or genetic testing. Having these precursor conditions may mean there is an increased risk of having a blood cancer in one’s lifetime. Andrew Brunner, MD specializes in evaluating individuals who may have these precursor conditions or who have been diagnosed with them. He works with patients to understand their risk of disease progression and also discuss therapeutic implications of these conditions.

Precursor blood conditions include:

Clonal hematopoiesis of indeterminate potential (CHIP)

In CHIP, blood cells acquire mutations that are also seen in certain types of leukemias. Individuals with CHIP don't have symptoms or obvious abnormalities in their blood counts. However, research has shown that CHIP increases the risk of later in life developing a blood cancer, such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or myeloproliferative neoplasms (MPNs). The chance of CHIP turning into a blood cancer is about 0.5-1% per year.

Clonal cytopenias of undetermined significance (CCUS) and Idiopathic cytopenias of undetermined significance (ICUS)

Having unexplained low blood counts is called ICUS. Individuals with ICUS who also have mutations similar to those observed in CHIP are classified as having CCUS. The risk of developing myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or myeloproliferative neoplasms (MPNs) is higher in CCUS than in CHIP alone.

Program Physicians

Andrew Brunner, MD
- Hematology/Oncology
- Department of Medicine
Tim Graubert, MD
- Director, Hematologic Malignancy Program

Genetic Testing FAQs

Request an Appointment or Referral

Contact us to make an appointment with our team at the Hereditary Hematologic Malignancy Genetics Program.

617-724-1971

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