Thursday, March 13, 2008

Interview with Blanche Alter, MD

This is from the NCI DCEG Linkage newsletter April 2001

Hematologist Blanche Alter, Ph.D., M.P.H., took a couple of unusual turns before landing in the Clinical Genetics Branch (CGB) as a cancer expert this past August. A Harvard-trained pediatric hematologist, Dr. Alter focused on clinical oncology in the 1990's, when she headed the Division of Pediatric Hematology and Oncology for the University of Texas Medical Branch in Galveston, Texas. When changing circumstances threatened to leave her with an enormous clinical oncology load and little time to pursue her research, Dr. Alter chose a path less traveled: after a career that had begun in the late 1960's, she went back to school to earn an M.P.H.

DCEG Linkage caught up with Dr. Alter to talk about her plans now that she has joined CGB as a cancer expert.

Why did you choose to go back to school rather than simply look for another position?
I decided to explore ways in which my clinical and laboratory experiences in hematology and oncology might be used in a different and challenging manner. I started looking online at catalogs for schools of public health and discovered I was very interested in all the courses, particularly biostatistics, cancer, and genetic epidemiology. Many of the clinical reviews I had done of rare hematologic syndromes were really epidemiologic in their focus.

How did you decide to take your course work at Johns Hopkins University School of Public Health?
I have a history with Johns Hopkins. Although I did my undergraduate and specialty work in Boston at Radcliffe College and later at Harvard Medical School, I received my medical degree and my pediatric training at Johns Hopkins University. Most of the people I respected told me to go to Johns Hopkins University School of Public Health. One of the faculty there shared my interest in cancer progression in patients with genetic hematologic diseases. Unfortunately, he left shortly after I arrived!

Did you have to change your plans and find a new advisor?
No. That person had several graduate students and came back to Hopkins to meet with them.
I'm here at NCI because of a collaboration with Dr. Mark Greene, Chief of CGB. For my project at Johns Hopkins, I studied patients with Fanconi's anemia. Because medicine has improved our management of their usual problem, aplastic anemia, we've discovered that these patients are living long enough to get specific types of cancer at unusually early ages. But my interest goes beyond patients with Fanconi's anemia. Patients with a number of different "benign" hematologic diseases are at an increased risk for cancer as they get older. We're seeing that we can predict the types of cancer they're likely to get. Here at NCI, I plan to explore this propensity for cancer in patients thought to have these so-called benign diseases.

Do you mean these patients are likely to get other blood-related cancers as they get older?
They get leukemia, but they are likely to get solid tumors as well. For example, Fanconi's anemia arises from a defect in DNA repair. Patients who have Fanconi's anemia are at risk of getting aplastic anemia, acute myeloid leukemia, oropharyngeal and esophageal cancers, and gynecologic cancers like cervical and vulvar cancer.
But it's not quite that simple. Sometimes the bone marrow disease in these patients is cured because they've undergone bone marrow transplantation. We have to look at what roles immunosuppression and graft-versus-host disease may play in the development of these cancers. In addition, we plan to look at the rest of the families to establish the cancer risk among heterozygotes.

Are these patients more susceptible to human papillomavirus infection?
That's one possibility. We are definitely going to look at viruses and whether they are present in these tumor biopsies. But these cancers can also arise without human papillomavirus infection. Whatever turns out to be true, we are going to learn something about cancer pathways.
I'm also looking at patients who have Diamond-Blackfan anemia, a pure red cell aplasia. At least half a dozen of these patients have developed osteogenic sarcoma as well as leukemias and other cancers. Patients with dyskeratosis congenita, an X-linked disorder, often develop oropharyngeal and gastrointestinal cancers similar to patients with Fanconi's anemia. Patients with Shwachman-Diamond syndrome often go on to develop aplastic anemia and leukemia.

How far along is your project?
I'm still trying to get all the collaborators on board. Our patients suffer from multisystem diseases. When we bring patients in, many different specialists will need to meet with them. We also want to perform extensive laboratory evaluations to understand carcinogenesis in these disorders. Eventually, we will bring in one new family a week to the Clinical Center for the study. We also plan a larger study of patients that will not come to the Clinical Center, but who will provide epidemiologic information and laboratory and tumor biopsy materials. I am still at the review stage, which will be followed by full protocol development.
By Lisa Chiu