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Targeting PI3Kdelta in Childhood Acute Lymphoblastic Leukemia

Children’s Hospital Los Angeles
Yong-mi Kim, MD & Nora Heisterkamp, PhD
Grant Type: 
Reach Grants
Year Awarded: 
Type of Childhood Cancer: 
Acute Lymphoblastic Leukemia (ALL)
Project Description: 

The Samantha Hill Childhood Cancer Hero Reach Grant


Although many children who are treated for acute lymphoblastic leukemia (ALL) are cured, a significant percentage are not, and when this happens the prognosis is grim. Therefore, we need new ideas for the treatment of relapsed ALL. Instead of targeting only the leukemia cells, we look at a wider target: the leukemia cells as well as the protective non-leukemia cells, which are located in the bone marrow and create a safe haven for ALL cells.

When leukemia cells attach to bone marrow cells, a protein called PI3Kd triggers pro-survival signals inside the leukemia cell. Using an inhibitor of PI3Kd, we showed that this drug kills ALL cells and, importantly, makes them more sensitive to chemotherapy. We also developed a clinically useful method to track PI3Kd activation.

Project Goal

We propose preclinical studies to determine how PI3Kd inhibition could be used to optimally treat relapsed ALL. We aim to:

  1. Find if there are certain subtypes of ALL that would benefit more than others from this treatment
  2. Find how it kills ALL cells
  3. Refine a test to monitor drug treatment in clinical trials.

Positive results of this evaluation of PI3Kd inhibition in ALL will be followed by a clinical trial in patients with ALL, done in conjunction with a clinical trial consortium, TACL, headquartered at Children's Hospital Los Angeles.

These studies were inspired by the knowledge that the FDA has approved a drug for the treatment of a type of leukemia typically found in older people, but which affects a related type of blood-forming cells in pediatric acute lymphoblastic leukemia. We have recently published the results of our experiments that were seeking to determine if we could use this drug, or others that inhibit the same target, to treat childhood leukemia. The studies show that this drug has an effect against some of the leukemia samples, and in particular if it is combined with standard chemotherapy. We are continuing to negotiate with the biotechnology company Gilead, which makes this drug for the treatment of adult leukemia, to obtain it for treatment of children in a multi-center consortium, TACL (Therapeutic Advances in Childhood Leukemia) that is headquartered at Children’s Hospital Los Angeles. The drug we are studying is known to have a specific “target”, meaning that the drug interferes with the action of a specific protein that helps the pediatric leukemia cells to survive. We also are working on alternative strategies (testing drugs) to attack the same “target”. These other drugs may have a stronger effect on the target, which could lead to a more potent anti-leukemia effect.

*See Samantha's hero story.