Hematological Malignancies Program

The Hematological Malignancies Program (HMP) continues a long tradition of leukemia research in the Cancer Center at St. Jude Children’s Research Hospital, facilitating interdisciplinary collaborations in basic, clinical and translational research related to the pathogenesis and treatment of childhood leukemia. The overall goal of the Hematological Malignancies Program is to advance cure rates for children with leukemia, while minimizing acute and late sequelae of therapy. Five major areas of research focus have been developed within the program:

  • innovative clinical trials
  • leukemia biology and minimal residual disease detection
  • pharmacogenomics and drug metabolism
  • pharmacodynamics and experimental therapeutics
  • late effects of treatment

Substantial progress has been made in advancing the cure rates of leukemia, in elucidating molecular mechanisms of leukemogenesis, in revealing new dimensions of pathologic features of leukemic cells and mechanisms of drug resistance using global gene-expression profiling, in refining methods to detect minimal residual disease, in optimizing treatment using pharmacokinetic and pharmacodynamic principles, and in elucidating host genetic determinants (i.e., pharmacogenomics) of treatment responses and late effects. These findings have been consistently translated into clinical research protocols to evaluate treatment innovations and improve outcome. Despite impressive progress, the need for further advances is inarguable. The HMP remains focused on research that will further improve the cure rate while reducing morbidity.

The HMP was formally established within the St. Jude Children's Cancer Center in 1995, although it has functioned as an interactive, multidisciplinary program for several decades at St. Jude. Currently, the HMP membership includes five department chairs and represents 10 different academic departments and 3 divisions, with leukemia research spanning from mouse and human genetics to prospective clinical trials.

In addition to conducting innovative clinical and translational trials at St. Jude, HMP members have also been active in the Children’s Oncology Group (COG), sitting on committees and serving as advisors or Principal Investigators for COG protocols. HMP members were founding members of the International acute lymphoblastic leukemia (ALL) Working Group, coordinating many international collaborative research. HMP members have also developed and led a multi-institutional protocol for children with acute myeloid leukemia (AML02), in collaboration with Stanford, Dana Farber, Children’s Hospital of Michigan, Children’s Hospital and Regional Medical Center in Seattle, and Cook’s Children Medical Center. Thus, HMP members engage in single-institution clinical and translational protocols when appropriate to address questions that require the immediate interface of clinics and labs (e.g., ALL), or in multi-institutional collaborative protocols when patient numbers or research objectives dictate (e.g., AML). Moreover, HMP members have been leaders in a Pharmacogenetics Research Network funded by a U01 supported by NCI and NIGMS, with the St. Jude team focusing on pediatric leukemia and a team from the University of Chicago focusing on adult cancers.

Investigators in the HMP will continue to focus on research initiatives that fully capitalize on the unique resources and environment of our Cancer Center, with an emphasis on studies that require uniform treatment of children at a single institution where laboratory and clinical studies can be readily integrated. Our strengths lie in our ability to integrate basic scientists and clinical investigators in the design and conduct of clinical and translational research, to provide new insights into the etiology, prognosis and treatment of childhood leukemia. One example is our ongoing studies to study global gene expression and single-nucleotide-polymorphisms in normal host cells and leukemia cells in all new cases of ALL and AML, to elucidate new insights to the biological basis of heterogeneous responses to chemotherapy. Our long-term goal is to improve the treatment of childhood leukemia by developing more effective and less toxic treatment strategies. To this end, our research will continue to focus on (1) molecular characterization of malignant cells to develop more precise methods for diagnosis, risk assessment and monitoring; (2) optimization of therapy through clinical and cellular pharmacodynamic studies; (3) elucidation of molecular mechanisms governing inter-individual differences in drug metabolism and effects, as well as in drug resistance; (4) identification of effective new chemotherapeutic or biologic agents via in vitro model systems and clinical trials; (5) therapeutic intervention based on levels of minimal residual leukemia; and (6) exploitation of laboratory discoveries in the development of innovative treatment strategies.

Ching-Hon Pui, MD, and Charles Mullighan, MBBS(Hons), MSc, MD, are co-leaders of the program.