Mutations in Protein That Causes Certain Leukemia Identified

New understanding of the molecular mechanisms behind certain types of blood cancer helps design therapies to treat the disease.

Mutated proteins cause several types of leukemia, particularly chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML), both of which tend to have a poor prognosis as they progress to acute myeloid leukemia (AML). //

An existing drug might be repurposed to treat these leukemias, and the new understanding of the molecular mechanisms at work may offer clues to other drugs yet to be developed.

Chronic Myeloid Leukemia
Chronic myeloid Leukemia is one of the most common types of blood cancer. It is characterized by excess of WBC stem cells in the bone marrow.

‘Mutations in a protein network drive several high-risk leukemias, offering new prospects for novel therapies.’

A team led by Wei Tong, PhD, a hematology researcher at Children's Hospital of Philadelphia (CHOP), investigated a well-known kinase, or signaling protein, called JAK2, which plays a key role in the development of blood-forming cells in bone marrow.

If something disrupts the normal regulation of JAK2 activity, JAK2 triggers the uncontrolled growth of marrow cells that give rise to a myeloid leukemia. Until now, the molecular events that regulate JAK2 were poorly established.

Based on studies in animals and in primary human leukemia cells, Tong and colleagues now report that mutations in either of two proteins, CBL and LNK/SH2B3, form a complex with JAK2 to disrupt JAK2 regulation and cause leukemia.

Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia (CLL) is one of the most common types of adult leukemia and is considered as one of the ‘good cancers’.

"This research has major implications for leukemia patients," said Tong. "A drug called ruxolitinib inhibits JAK2 and is already approved by the Food and Drug Administration. Our studies in cells from leukemia patients strongly suggest that patients with mutations in any of the three proteins could benefit from ruxolitinib."

She added that clinical research should test whether this drug can benefit patients with CMML and JMML, as well as AML patients who have CBL mutations.

Acute Myeloid Leukemia-Causes-Symptoms-Diagnosis-Treatment-Prognosis-FAQs
Acute myeloid Leukemia, more popularly known by its abbreviated form AML, is a fast- evolving leukemia that affects both children and adults alike

In addition to the potential benefits of ruxolitinib, Tong said, the team's findings may lead researchers to develop novel leukemia drugs aimed at mutations in any of the three proteins in a precision medicine approach.

"As we continue to discover that specific mutations may cause subtypes of cancer, learning the underlying molecular mechanisms provides opportunities to develop targeted treatments."

Acute Lymphoblastic Leukemia - Incidence Causes Symptoms Diagnosis Treatment Prognosis
Acute lymphoblastic leukemia (ALL) is the cancer of white blood cells characterized by excess lymphoblasts. It is the most common of all childhood cancers and can be fatal in weeks if left untreated.

Source-Eurekalert