Late last April, Rita Gist was feeling tired—“just a little off.” Worried that she had COVID-19, the 36-year-old Bronx mother of three promptly set up an appointment through Montefiore with her primary care doctor. Blood tests revealed the true cause of her fatigue: Ms. Gist had acute myeloid leukemia (AML), a potentially deadly form of blood cancer. Within 24 hours of her diagnosis, she was undergoing the first of several rounds of treatment.
Breakthroughs in Care
For decades, treatment for AML and the dozens of other types of blood cancer was largely limited to a few chemotherapy drugs that killed healthy and cancerous cells alike, says Aditi Shastri, M.D., assistant professor of medicine and of developmental & molecular biology at Einstein, a member of the Albert Einstein Cancer Center (AECC), and one of Ms. Gist’s Montefiore oncologists. The drugs caused severe side effects and ultimately weren’t very effective against cancers such as AML.
However, about 20 years ago, advances in genetic sequencing led to breakthroughs in care. “We realized that a big part of why people get blood cancer is because genetic mutations cause blood cells to develop abnormally,” Dr. Shastri says. In particular, the origin of many cancers can be traced to mutations in hematopoietic stem cells (HSCs)—cells residing in the bone marrow that are responsible for producing all of the body’s blood cells.
“Those discoveries have allowed us to design treatments that specifically target cancer-causing mutations in stem cells,” Dr. Shastri says. Ms. Gist takes a drug that inhibits the mutations that occur in about one-third of AML cases, including hers. And last September, she underwent a stem-cell transplant: Doctors wiped out the cancerous leukemic cells throughout her body with chemotherapy and then infused bone marrow donated by her mother, which contained healthy stem cells. “So my mom gave life to me two times,” Ms. Gist says with a laugh.
Einstein has made a huge commitment to gender and racial diversity that has had a measurable impact on the careers of female scientists at every experience level.
Britta Will, Ph.D.
Women Leading Research
Scientists and physicians at the AECC are at the forefront of efforts to prolong the length and quality of life for patients like Ms. Gist and are leading research to understand what causes mutations and how to prevent them.
“The real strength of the program is the collaborative spirit among world-class researchers and clinicians,” says Ulrich Steidl, M.D., Ph.D., co-director of the Blood Cancer Institute in the AECC along with Amit Verma, M.B.B.S. “It creates a unique ability to bring discoveries from the lab into the clinic.” Dr. Steidl is associate director for basic science research at AECC, professor of cell biology and of medicine, the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein, and the associate chair for translational research in oncology at Montefiore.
Dr. Shastri agrees and points to a culture that also fosters diversity and inclusion. While women make up more than half of medical school graduates, their numbers tend to drop off as you go up the ladder, she notes. “But here, I work with many women who are scientists and physicians and who are excelling in their careers,” she says. “That’s important to me.”
AECC researcher Britta Will, Ph.D., says people “can only work at the highest level if not constantly facing uphill battles. Einstein has made a huge commitment—not just on paper—to gender and racial diversity that has had a measurable impact on the careers of female scientists at every experience level.”
As a result, Dr. Verma says, the AECC has attracted a number of women who are leaders in the field of blood cancers. “Having colleagues who are exceptional scientists and clinicians doing important basic and clinical research is very inspiring. These rising superstars are being noticed nationally and even internationally in their respective fields,” he says. Dr. Verma is the associate director for translational research at AECC, professor of medicine and of developmental and molecular biology at Einstein, and director of hemato-oncology at Montefiore.
Prominent women involved in HSC research include (in alphabetical order):
Lizamarie Bachier Rodriguez, M.D., assistant professor of medicine at Einstein and an oncologist at Montefiore. Dr. Bachier Rodriguez is investigating ways to improve outcomes for blood-cancer patients. She’s studying the experience of patients like Ms. Gist, who receive “haploidentical,” or half-matched, bone marrow transplants from a parent, sibling, or child who share half the patient’s genes. “Currently, there’s little data on how patients in a multi-ethnic inner city fare with these type of transplants,” Dr. Bachier Rodriguez says.
She’s also working with physical therapy and nursing teams to see how factors such as exercise affect transplant patients. “We’re looking at how we can improve patients’ experiences and, ultimately, outcomes,”she says.
Teresa Bowman, Ph.D., associate professor of developmental & molecular biology and of medicine at Einstein. Dr. Bowman’s lab focuses mainly on myelodysplastic syndromes (MDS), a form of blood cancer in which the bone marrow produces too many immature blood cells that crowd out normal adult versions. About one-third of MDS cases evolve into AML. “By the time MDS becomes clinically evident, the patient has had the disease for a long time,” Dr. Bowman says. “We are trying to look at the earliest steps where mutations first change the function of blood cells.”
Dr. Bowman studies zebrafish, which have a lot in common with people when it comes to blood problems: The same genetic mutation that is found in 60% of MDS patients causes similar blood abnormalities in zebrafish. Her lab is screening more than 700 drug compounds on zebrafish carrying the mutation, hoping to identify a compound that can counteract the effects of MDS.
Kira Gritsman, M.D., Ph.D., associate professor of medicine and of cell biology at Einstein and an oncologist at Montefiore specializing in blood cancers. Dr. Gritsman studies the signaling pathways that transmit messages within cells, ultimately reaching the genetic material in the nucleus. “How those messages are processed affects the decisions cells make—about whether to proliferate, for example, or to differentiate into a more mature cell type,” she says. “Our lab focuses on the PI3 kinase (PI3K) signaling pathway, one of the most commonly mutated pathways in cancer.”
The PI3K pathway is overactive in up to 80% of patients with AML, the blood disease affecting Ms. Gist. An overactive PI3K pathway is essential for the survival of leukemic stem cells, helping them resist chemotherapy and leading to relapses of the disease. “There are actually several drugs already approved for treating other cancers that work by inhibiting the PI3K pathway,” Dr. Gritsman says. “Our goal is to figure out whether any of those drugs can be used safely and effectively against AML.”
Aditi Shastri, M.D., assistant professor of medicine and of developmental & molecular biology at Einstein and an oncologist at Montefiore. Dr. Shastri studies gene mutations that fuel the transformation of blood cells into blood cancers. She is focusing on the gene that codes for signal transducer and activator of transcription 3 (STAT3), a protein essential for normal blood cell development but that is expressed at abnormally high levels in blood cancers. “We are targeting STAT3 and a few other proteins in preclinical studies and early-phase clinical trials here at Einstein,” Dr. Shastri says.
Dr. Shastri is also committed to the National Institutes of Health’s mission to diversify clinical trials. Globally, she points out, more than 90% of the enrollees in clinical trials are white. “Albert Einstein Cancer Center is unique in that we provide access to state-of-the-art trials to a traditionally underserved population,” she says. “In 2019, 80% of our participants in blood cancer trials were Black or Hispanic.”
Britta Will, Ph.D., assistant professor of medicine and of cell biology at Einstein. AML, MDS, and other cancers develop primarily in older people. Yet for decades, Dr. Will says, the research approach taken by scientists has largely ignored aging as a factor in how cancer develops. “We are trying to understand the molecular and functional decline that occurs in aging HSCs,” she says. “The next step is to explore how these changes may contribute to the evolution of cancer. We would like to develop targeted therapies that prevent those age-related changes from affecting cancer stem cells but that don’t harm healthy stem cells.”
In addition, Dr. Will’s lab studies the role of iron in the development of blood cancers. She has discovered that iron, which is crucial to the function of cancer cells, builds up in aging stem cells. “We’re now studying whether alterations in how HSCs handle iron and molecular recycling (turnover) during aging contribute to the development of stem-cell-derived blood cancers,” she says.
B. Hilda Ye, Ph.D., associate professor of cell biology at Einstein. Dr. Ye studies how B cells (white cells that produce antibodies) and T cells (white cells that defend the body against infection and cancer) mature into functioning cells and where that maturation process goes awry and leads to lymphomas. In particular, she’s interested in a rare, aggressive form of lymphoma called adult T-cell leukemia/lymphoma (ATLL). The disease is linked to infection with a retrovirus endemic in Japan, the Caribbean, and parts of South America. “Because the Bronx is home to a large number of immigrants from the Caribbean region, it is one of the best places in the U.S. to study ATLL,” she says.
Dr. Ye’s lab is investigating a nuclear enzyme called P300 that influences how cells read the genetic information in DNA. Mutations in the gene that codes for P300 suppress the enzyme’s activity in the North American version of ATLL. Yet, these mutations are found infrequently in the Japanese variant of the disease. “We are looking at whether these mutations help precancerous T cells develop into full-blown ATLL,” she says, “and whether this knowledge can lead to novel therapies for our patients.”
Hope for a Cure
Thanks to her treatments, Ms. Gist’s cancer is in remission, and she has resumed life as a busy mom. “Sometimes I forget that I’m even going through this, I feel so good inside,” she says. Ms. Gist hopes her story shows that “just because you are diagnosed with AML, or another cancer, does not mean that life is over.”
She is thankful for her doctors’ compassion—“Dr. Shastri is my angel,” she says—and optimistic about her future. “My hopes and dreams are that they find a cure,” Ms. Gist says. “The studies, clinical trials, and everything? I’m here for it. This disease is scary. I’m just happy that they aren’t giving up.”
Posted on: Wednesday, February 10, 2021