Category: Laboratory Research

Waldenstrom’s Macroglobulinemia Clinical Database Study

The purpose of this study at Weill Cornell Medical College is to learn about what might cause lymphoma, to learn about how lymphoma harms the body, and to learn about treatments for Waldenstrom’s Macroglobulinemia.

This study is open to people being treated for Waldenstrom’s Macroglobulinemia outside of NewYork-Presbyterian/Weill Cornell, but participation would require at least one visit at Weill Cornell.

Waldenstrom’s Macroglobulinemia is a rare type of lymphoma, a disease where one of the white blood cells, the lymphocytes, increases in number more than they should. The lymphocytes in Waldenstrom’s Macroglobulinemia also secrete a protein called IgM. Excess IgM can interfere with the circulation of blood. Investigators at Weill Cornell Medical College and other institutions are collecting information about lymphoma patients and their disease, as well studying their lymphoma cells in the laboratory.

Participants in this study give their permission for the investigators to collect their clinical information for research purposes. In addition, the researchers will store participants’ blood, urine, check swab, bone marrow and/or tumor tissue samples for research studies to be performed now and in the future. In some cases, participants may be asked by their physician to provide additional samples.

By studying the clinical course of lymphoma patients and the lymphoma cells in the laboratory, we hope to learn more about what causes lymphoma. We also hope that information from these studies will help identify new treatments for people with lymphoma.

To find out more about this study please contact June Greenberg, RN at (212) 746-2651 or email June at jdg2002@med.cornell.edu.

The principal investigator of this study is Dr. Peter Martin. Click here to read Dr. Martin’s clinical and research profile.

Weill Cornell Researcher: A Personalized Approach for Targeting Cancer Tumors

Through a collaboration between researchers at Weill Cornell Medical College, Memorial Sloan-Kettering, and the National Cancer Institute, researchers have reported that a tumor-targeting compound called PU-H71 can reveal with great accuracy the set of altered pathways that contribute to malignancy, thus allowing physicians to “fish-out” entire networks of abnormal proteins in tumor cells.

One major obstacle in the fight against cancer is that anticancer drugs often affect normal cells in addition to tumor cells, resulting in significant side effects. Yet research into development of less harmful treatments geared toward the targeting of specific cancer-causing mechanisms is hampered by lack of knowledge of the molecular pathways that drive cancers in individual patients.

“A major goal of cancer research is to replace chemotherapy with drugs that correct specific molecular pathways disrupted by cancer,” said Weill Cornell’s  Dr. Ari Melnick, one of the study’s lead investigator. The research was published in Nature Chemical Biology.

The researchers have uncovered that PU-H71 can reveal, with great accuracy, the set of altered pathways contributing to malignancy, thus allowing physicians to “fish-out” entire networks of abnormal proteins in tumor cells. PU-H71 binds to these abnormal protein complexes which are part of protein networks supporting cancer cell growth, division and survival. This knowledge could lead to more targeted, effective and individualized therapies for the personalized treatment of cancer – a disease in which no two tumors are alike – while producing fewer side effects and ultimately sparing patients from undergoing chemotherapy.

Based on these findings Dr. Melnick and colleagues have received a multi-investigator collaborative grant from the National Cancer Institute in support of clinical trials for the treatment of cancer. Currently, patients are being recruited for the first clinical trial to test the safety of PU-H71 as a drug used for the treatment of a variety of tumors. Subsequent trials will include patients with cancers such as breast, lymphomas, and chemotherapy-resistant leukemia.

Lymphoma in the News: Two Important Studies Take Us One Step Closer to Personalized Lymphoma Therapy

By Peter Martin, MD and Olivier Elemento, PhD

Based on multiple randomized phase 3 studies initiated over a decade ago, R-CHOP chemotherapy is the standard of care for first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL). However, sometimes R-CHOP is not successful. Fortunately, our understanding of lymphoma has evolved over the past decade.

It is increasingly clear that “DLBCL” is a heterogeneous group of related tumors. Studies using gene expression profiling [1], have revealed that DLBCL can be divided into three subgroups based on the probable cell of origin (i.e., the cell from which the lymphoma was derived): activated B-cell like DLBCL (ABC), germinal center-like DLBCL (GCB), and a third group, termed “type 3”, that doesn’t possess any specific characteristics (click here to read the abstract). So far, the clinical relevance of differentiating between the ABC and GCB subtypes of DLBCL remains somewhat unclear. Nonetheless, studies done at Weill Cornell Medical College and elsewhere have suggested that certain treatments might preferentially benefit one subtype (see here and here). As a result, ongoing clinical trials are evaluating newer therapies targeted to the appropriate subgroup.

Just as we are beginning to understand the significance of DLBCL gene expression profiles, recent technological advances in DNA sequencing are making the rapid, high-resolution sequencing of a tumor’s entire genome (DNA code) possible and affordable [2]. Two recently published papers describe the results of long-term efforts by two different groups to sequence the genome of DLBCL tumors.

A Groundbreaking Study

In a paper entitled “Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma” published in the journal Nature, Gascoyne, Marra and colleagues describe the results of a groundbreaking study. The researchers sequenced the entire DNA code from lymphoma tumors and compared the results to normal DNA obtained from the same patients. They were able to identify several genes that were mutated in the tumors but not in the normal DNA. Using these data, they were able to identify 109 genes with a potential role in lymphoma. Continue reading “Lymphoma in the News: Two Important Studies Take Us One Step Closer to Personalized Lymphoma Therapy”