Brief Biography

Dr. Hans Hitzler is a clinician scientist in the Division of Haematology/Oncology, at The Hospital for Sick Children (SickKids) and a member of the division's Leukemia/Lymphoma Section. He is also Scientist in the Developmental & Stem Cell Biology program at SickKids Research Institute and an Assistant Professor of Paediatrics at the University of Toronto .

Dr. Hitzler received his medical training at the University of Ulm in Germany (1980-1986). Following a research fellowship at the Ontario Cancer Institute, Hitzler completed a paediatric residency and fellowship in paediatric hematology/oncology in Toronto at SickKids. After a post-doctoral research fellowship with at St. Jude Children's Research Hospital in Memphis, he joined the Division of Haematology/Oncology at SickKids in 1998.

His research interests are the genetic mechanisms underlying childhood leukemia. In 2001 Dr. Hitzler reported, with colleagues at St. Jude Children's Research Hospital, the discovery of two novel genes that play an important role in the acute megakaryoblastic leukemia of children. He currently studies the role of GATA1 mutations in acute myeloid leukemia of children with Down syndrome.

Hitzler was the recipient of the Department of Paediatrics Junior Faculty Award for Excellence in Research in 2003. In 1999 and 2008 he received the Division's Alvin Zipursky Teaching Award in recognition of outstanding contributions to education and mentorship.

Clinical Care Activities

My main clinical interest is the diagnosis and treatment of leukemia and lymphoma in children. I have a particular interest in the leukemic disorders that occur in children with Down syndrome and relapsed acute lymphoblastic leukemia.

Academic Background

Paediatric Hematology/Oncology Fellowship
The Hospital for Sick Children, 1993-06-01 - 1995-06-01

Research Interests

My main research interests have been in the genetic events leading to acute leukemia with a focus on acute megakaryoblastic leukemia, a form of leukemia that is frequently seen in infants and in children with Down syndrome.

The focus of my research interest is the genetic mechanism underlying acute megakaryoblastic leukemia (AMKL). We identified the fusion of two novel genes, RBM15 and MKL1, as the molecular mechanism of the major chromosomal translocation found in AMKL of infants, t(1;22)(p13;q13). We are currently studying the role of GATA1 mutations in AMKL and its precursor, Transient Leukemia (TL), of children with Down syndrome. The focus of our work is on functional studies of leukemia-initiating cells in AMKL and TL.

Research Activities

The focus of my research interest is the genetic mechanism underlying acute megakaryoblastic leukemia (AMKL). We have recently identified the fusion of two novel genes, RBM15 and MKL1, as the molecular mechanism of the major chromosomal translocation found in AMKL of (non-Down syndrome) infants, t(1;22)(p13;q13). The focus of our current work is to define the mechanism of action of the fusion protein and the physiologic role of the wildtype proteins during hematopoiesis. future: Our aims are to define the structural domains relevant for the function of the fusion protein in AMKL, to assess the effect of the fusion protein on hematopoiesis in vivo, and to define the role of the wildtype proteins by gene inactivation.

External Funding

• NCIC
• NIH
• Genome Canada
• Leukemia Lymphoma Society

Publications

Shah N, Al-Ahmari A, Al-Yamani A, Dupuis L, Stephens D, Hitzler J: Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children with Down syndrome, Pediatric Blood and Cancer 2008 Sep 18. [Epub]

Almanjomi F, Armstrong D, Abla O, Naqvi A, Weitzman S, Hitzler J: Lumbar spinal fluid collections in children treated with intrathecal chemotherapy- elevated CSF protein as a diagnostic clue. Pediatric Blood and Cancer 2008 51(2):295-8.

Zwaan CM, Reinhardt D, Hitzler J, Vyas P: Hematological diseases in children with Down syndrome. Pediatric Clinics of North America 2008 Feb;55(1):53-70.

Hitzler, JK: Acute megakaryoblastic leukemia in Down syndrome. Pediatric Blood and Cancer 2007 Dec 49(7 Suppl): 1066-9.

Spiegler BJ, Kennedy K, Maze R, Greenberg ML, Weitzman S, Hitzler JK, Nathan PC: Comparison of long-term neurocongnitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate. Journal of Clinical Oncology 2006:24(24):pp3858-64.

Ahmari A, Shah N, Sung L, Zipursky A, Hitzler J: Long-term results of a ultra low dose cytarabine-based regimen for the treatment of acute megakaryoblastic leukemia in children with Down syndrome. British Journal of Haematology. 2006 Jun 133(6): 646-8.

Hitzler JK, Zipursky A: Origins of leukemia in children with Down Syndrome. Nature Reviews Cancer 2005: 5 (1): pp 11-20.

Lightfoot J, Hitzler JK, Zipursky A, Albert M, Macgregor PF: Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome. Leukemia 2004: 18 (10): pp 1617-23.

Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A: GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood 2003: 101 (11): pp 4301-4.

Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer, Hitzler JK: Fusion of two novel genes, RBM15 and MKL1, in the t(1;22) (p13;q13) of acute megakaryoblastic leukemia. Nature Genetics 2001: 28: pp 220-221.