Taking Direct Aim at AML

If you spend much time reading grant applications, especially if you are a layperson and not among the cognoscenti, you are often surprised by the requirements one must meet before even beginning to write. For example, from the application for the Leukemia & Lymphoma Society Scholar Award: “You must be a highly qualified investigator who's shown a capacity for independent, sustained original investigation in the field of hematologic malignancies. You should hold an independent faculty-level or equivalent position and have obtained substantial support for your research from a national agency.” The prize, however, is worth the effort: Five years of salary and benefits.

Such is the position in which Ravindra (Ravi) Majeti, MD, PhD (assistant professor, hematology), finds himself beginning July 1, 2015. For the next five years he doesn’t have to worry about submitting salary support grants for himself, leading this reporter to ask him whether or not he is relieved to forgo the task for the near future.

“It’s a great award with an incredible amount of financial support that I’m honored to have received,” he said, “and it does make things easier, but the reality is that to run a lab like the one that I lead I need to raise, counting salaries, something like $1.5 to $2 million a year. There’s always a lot of grant writing.”

Majeti’s CAP Profile talks about his research into acute myeloid leukemia (AML), searching for ways to eradicate the leukemia stem cells that permit AML to happen while preserving normal stem cells. Having found that one particular protein marker on the surface of leukemia stem cells – CD47 – is a culprit in AML, he and his colleagues have aimed to develop a therapy to interfere with the actions of CD47.

What Majeti’s CAP Profile does not yet talk about is the last several years of progress in this research. He explains it this way: “We have embarked on a massive undertaking inside the University. We manufactured a drug that targets the CD47 molecule and we have an open active clinical trial at Stanford. We did basically what a startup biotech company would do, but we got some unique grant-type funding to allow us to do it all inside the University. It’s been a new experience both for the University and for us as researchers.”

The current Phase I study in patients with solid tumors is looking at safety and dose-finding rather than efficacy, although, as Majeti says, “we will also measure tumor responses. The AML patients will be coming along later this year.”

The Majeti lab, while clearly focused on the development of this promising therapy, is not without other projects aimed at better understanding AML and making progress toward its treatment and ultimately its eradication. One approach is looking at recurrent genetic mutations in AML with the hope of functionally characterizing them, determining their role in the development of AML, and creating new therapies based on this new knowledge. Another project capitalizes on the long-lived and self-renewing nature of hematopoietic stem cells (HSC) to isolate residual cells in blood and marrow samples obtained from patients at the time of AML diagnosis. “By demonstrating that the residual HSC contained some but not all of the leukemic mutations,” says Majeti, “we found evidence supporting our hypothesis” that mutations must be serially acquired in clones of HSC. This research may help identify the source of relapsed disease that causes significant mortality in this deadly disease.

With such promising progress under way early in a career, and with salary support in hand until 2020, what are Majeti’s hopes for his future?

“My long-term goal is to make an impact on outcomes of patients with AML. That’s my personal mission and vision. We are treating them with same crappy chemotherapy drugs that were being used in the 1980s, and patients don’t do well. We need to bring them new approaches.”