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Researchers attempt new treatment approach for blood cancer

June 19, 2020

(Boston)--In an effort to improve the survival of patients with myeloproliferative neoplasms, a type of leukemia, researchers inhibited a specific protein (alpha5beta1 integrin) to decrease the number of large bone marrow cells (megakaryocytes) in an experimental model. An increase in megakaryocyte numbers is thought to be the cause of many problems observed in this disease. This type of treatment approach has never been attempted before.

Myeloproliferative neoplasms are a type of blood cancer that begin with a pathological mutation (change) in a stem cell in the bone marrow which causes too many red blood cells, white blood cells, or platelets to be produced. Most patients die of transformation of the disease to a more fatal leukemia or because of myelofibrosis, a scarring of bone marrow. There are currently no specific treatments for myelofibrosis.

"To date, most drug development efforts have been focused on the JAK2V617F mutation, but this approach has failed to fundamentally change the course of disease. Our study has taken a totally new approach for treatment of the disease, which, if successful, will present a complementary or even an alternative therapy to existing treatments," explained lead author Shinobu Matsuura, DVM, PhD, instructor of medicine at Boston University School of Medicine (BUSM).

Using two sets of experimental models, the researchers altered the JAK2V617F gene in one group to induce symptoms of myeloproliferative neoplasms. The second group were the control. When both groups were exposed to an antibody against alpha5beta1 integrin, the number of megakaryocytes decreased in bone marrow in the group with the altered gene, while no changes were seen in the control group.

According to the researchers, their ultimate objective is to find effective treatments for myelofibrosis, which can occur secondary to many diseases and is a terminal condition with no specific treatment available."Myeloproliferative neoplasms are a chronic and debilitating disease. Safe and effective novel treatments of this disease will improve the quality of life of these patients."
-end-
These findings appear online in the journal Blood.

Funding for this study was provided by NIH NHLBI grant R01HL136363 to KR, and by Associazione Italiana per la Ricerca sul Cancro: AIRC IG 2016 18700 to AB and Italian Ministry of Health (Ricerca Finalizzata Giovani Ricercatori GR-201602363136) to AB. SM is supported by the NIH ORIP SERCA K01 award 1K01_D025290-01A1. CRT, SKN and CMW were supported by a Cardiovascular Research Training grant T32 HL007224, and CMW was further supported by Research in Blood Diseases and Resources Training grant T32 HL007501, both from the NIH NHLBI.

Boston University School of Medicine

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