SWCRF researcher John Crispino, Ph.D., publishes discovery of a promising new therapy for rare blood malignancies in Nature Medicine.


John Crispino, Ph.D.

The Samuel Waxman Cancer Research Foundation congratulates its funded blood cancer investigator John Crispino, Ph.D., who along with colleagues at the Robert H. Lurie Cancer Center at Northwestern University published in the leading science journal Nature Medicine their identification of a potential new treatment for primary myelofibrosis, a rare and incurable form of blood malignancy.

The drug, a compound known as Alisertib, causes bone marrow cells called megakaryocytes to mature and stop proliferating – a process known as differentiation. The researchers previously demonstrated the drug’s effectiveness in differentiating another rare blood malignancy – acute megakaryocytic leukemia – in research published in the journal Cell in 2012. This latest discovery harks back to SWCRF founder and CEO Dr. Samuel Waxman’s development of the breakthrough therapy for acute promyelocytic leukemia in collaboration with Drs. Zhen-Yi Wang and Zhu Chen of the Shanghai Institute of Hematology. Dr. Crispino’s fellow SWCRF researcher Ross Levine, M.D. of Memorial Sloan Kettering Cancer Center is a co-author on the Nature Medicine paper.

“We applaud the excellent work of John Crispino and his colleagues at Northwestern University,” said Dr. Waxman. “This exciting finding demonstrates the power of differentiation to make significant progress in the development of new, less-toxic therapies for blood malignancies, which is central to the SWCRF mission.”

There are approximately 15,000 patients with myelofibrosis in the United States today; they have an average life expectancy of five to seven years after diagnosis. Right now, there’s just one drug approved to help manage their symptoms, which can include fatigue, relentless fevers, bone pain and an enlarged spleen. There are no treatment options, apart from bone marrow transplantation, that can move the disease into remission.

In the study, the scientists found that Alisertib reduced tumor cells, blood counts and fibrosis in mouse models of the disease. The drug induces bone marrow cell differentiation by inhibiting Aurora kinase A, an enzyme encoded by the gene AURKA. The research team showed that AURKA had elevated activity in cell samples from patients with myelofibrosis and that the immature cells in the patients could be made to differentiate in culture.

Dr. Crispino and his colleagues Brady Stein, M.D., and Frank Giles, M.D., continue to research whether the drug can be a viable treatment for patients. Dr. Crispino is conducting correlative studies in the lab to see if patient samples of myelofibrosis respond to Alisertib the same way mouse models of the disease did. Meanwhile, Dr. Stein is recruiting participants for a phase I clinical trial investigating Alisertib for patients with myelofibrosis. Jessica Altman, M.D., co-director of the Lurie Cancer Center’s leukemia program, is investigating the drug in patients with megakaryocytic leukemia.

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