Category: Laboratory Research

Researchers Sequence Anaplastic Large Cell Lymphoma Genome Identifying Potential New Therapy Targets

Anaplastic lymphoma kinase-negative large cell lymphoma (ALCL) is a common form of T-cell cancer, accounting for 15% of all non-Hodgkin lymphoma cases in the United States. In a study published yesterday in Cancer Cell, senior author Dr. Giorigio Inghirami and an international team of researchers discovered the genetic mutations that drive tumor growth, potentially leading to new targeted therapies for T-cell lymphoma. They found,

“Massive sequencing data revealed that more than 38 percent of the tumors contained mutations in two genes, called JAK1 and STAT3. The researchers then examined the results when the genes were left intact and when they were blocked in cell cultures and in animals. They found that there was significantly less tumor growth when JAK1 and STAT3 were inhibited. JAK1 and STAT3 happen to reside along the same pathway, making them increasingly powerful to perpetuate harmful phenotypes once they are created. Dr. Inghirami likens this concept to a car (the cancerous cell) being propelled by gasoline (the mutations along a pathway that enable communication to continue).”

Said Dr. Inghirami,

“Now we have a class of drugs that will potentially work in this population…The interesting part is that pathway is now being found in different diseases – it looks like a recurring motif. So maybe we have the capacity to expand the therapeutic efficacy of this drug to others with similar phenotypes.”

Look to this space for more information about developments regarding treatments for ALCL and other T-cell lymphomas. Currently open clinical trials for T-cell lymphoma can be found here and here.

Classical Hodgkin Lymphoma Genome Sequenced by Research Team

In a recent study first published online, then as a plenary paper in the February 12 issue of Blood an inter-institutional team of researchers sequenced the genome of classical Hodgkin lymphoma (cHL). This sequencing allowed researchers to study the changes in proteins in individual patients, which could potentially lead to the development of new therapies targeting the cells affected by cHL. Their findings are especially notable as,

“Now we have a better idea of what mutations there are, and going forward therapies can be adapted to specific patient populations according to their genomic composition,” said senior author Dr. Ethel Cesarman, a professor of pathology and laboratory medicine at Weill Cornell Medical College.

Although scientists have sequenced the genomes of many other diseases, the cHL genome has remained elusive due to the difficulty of isolating Reed-Sternberg cells, which usually comprise less than 1 percent of a total cHL tumor. The team employed a technique that separates larger cells and looks at the proteins on their surface, called fluorescence-activated cell sorting, to successfully isolate the Reed-Sternberg cells and sequence the cancer genome, said senior author Dr. Mikhail Roshal, an assistant member in the Department of Pathology at Memorial Sloan Kettering Cancer Center.

These findings could potentially lead to more personalized treatment options for patients with cHL. They exemplify the bench to bedside approach taken by the Lymphoma Program and Meyer Cancer Center. Please look to this space for further updates about lymphoma news and clinical trials.

Palbociclib for Patients with Previously Treated Mantle Cell Lymphoma

Earlier this week the FDA granted accelerated approval to palbociclib for the treatment of advanced (metastatic) breast cancer in combination with letrozole. Palbociclib selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6), thereby suppressing tumor cell proliferation.

Over the past decade, researchers at Weill Cornell have led investigations of palbociclib in multiple myeloma and mantle cell lymphoma, including an ongoing phase I trial of palbociclib in combination with ibrutinib for patients with previously treated mantle cell lymphoma. Additional trials are planned.

Please look to this space for further updates concerning palbociclib for lymphoma patients. A full listing of available clinical trials can be found on our clinical trials page.