Donald Small, MD, PhD
Pediatric Hematology Oncology
Highlights
Johns Hopkins Affiliations:
- Johns Hopkins School of Medicine Faculty
About Donald Small
Professional Titles
- Kyle Haydock Professor of Oncology
Primary Academic Title
Professor of Oncology
Background
Dr. Donald Small is the Kyle Haydock Professor of Oncology. He holds joint appointments in Pediatrics and Cellular and Molecular Medicine and Human Genetics. He also directs the Johns Hopkins/National Cancer Institute Pediatric Hematology/Oncology Fellowship program.
Dr. Small received his undergraduate, and then M.D. and Ph.D. degrees from the Johns Hopkins University in 1979 and 1985. His Ph.D. research was conducted with Bert Vogelstein in the Oncology Department and his postdoctoral research with Tom Kelly in the Molecular Biology and Genetics Department. He trained in pediatrics and pediatric hematology/oncology at Johns Hopkins and joined the faculty in 1990.
Dr. Small’s laboratory was the first to clone the human FLT3 gene that is the most frequently mutated gene in acute myeloid leukemia (AML) and results in very poor chances of cure for these patients. The investigations of FLT3 led Dr. Small and his team to discover drugs able to inhibit the cancer-generating activity of this important gene. His laboratory showed that a new class of drugs known as tyrosine kinase inhibitors could kill FLT3-affected cells, thus developing one of the earliest molecularly targeted cancer therapies. They then developed a test that enabled them to screen a host of additional kinase inhibitors and find several with great potency against FLT3. His group also led the first clinical trials investigating the use of a FLT3 inhibitor in adult relapsed and refractory FLT3 mutant AML, and determined how best to combine these drugs with chemotherapy. They also helped design the first pediatric trials of FLT3 inhibitors in pediatric AML and infant ALL.
Dr. Small’s lab continues to investigate leukemic processes and the role of stem cells in governing the activities of the FLT3 gene in leukemia.
Centers and Institutes
Clinical Trial Keywords
FLT3 inhibitors; lymphoma; leukemia
Additional Academic Titles
Professor of Pediatrics
Research Interests
Development of leukemia and lymphoma and FLT3 mutations.
Selected Publications
- Brown, P.; Levis, M.; McIntyre, E.; Griesemer, M.; Small, D. Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner. Leukemia. 2006 Aug;20(8):1368-1376.
Kim, K.T.; Levis, M.; Small, D. Constitutively activated FLT3 phosphorylates BAD partially through pim-1. Br J Haematol. 2006 Sep;134(5):500-509.
Knapper, S.; Burnett, A.K.; Littlewood, T.; Kell, W.J.; Agrawal, S.; Chopra, R.; Clark, R.; Levis, M.J.; Small, D. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood. 2006 Nov 15;108(10):3262-3270.
Levis, M.; Brown, P.; Smith, B.D.; Stine, A.; Pham, R.; Stone, R.; Deangelo, D.; Galinsky, I.; Giles, F.; Estey, E.; Kantarjian, H.; Cohen, P.; Wang, Y.; Roesel, J.; Karp, J.E.; Small, D. Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood. 2006 Nov 15;108(10):3477-3483.
Piloto, O.; Nguyen, B.; Huso, D.; Kim, K.T.; Li, Y.; Witte, L.; Hicklin, D.J.; Brown, P.; Small, D. IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeficient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples. Cancer Res. 2006 May 1;66(9):4843-4851.
Radomska, H.S.; Basseres, D.S.; Zheng, R.; Zhang, P.; Dayaram, T.; Yamamoto, Y.; Sternberg, D.W.; Lokker, N.; Giese, N.A.; Bohlander, S.K.; Schnittger, S.; Delmotte, M.H.; Davis, R.J.; Small, D.; Hiddemann, W.; Gilliland, D.G.; Tenen, D.G. Block of C/EBP alpha function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations. J Exp Med. 2006 Feb 20;203(2):371-381.
Baldwin, B.R.; Li, L.; Tse, K.F.; Small, S.; Collector, M.; Whartenby, K.A.; Sharkis, S.J.; Racke, F.; Huso, D.; Small, D. Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease. Leukemia. 2007 Apr;21(4):764-771.
Brown, P.; McIntyre, E.; Rau, R.; Meshinchi, S.; Lacayo, N.; Dahl, G.; Alonzo, T.A.; Chang, M.; Arceci, R.J.; Small, D. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood. 2007 Aug 1;110(3):979-985.
Kim, K.T.; Baird, K.; Davis, S.; Piloto, O.; Levis, M.; Li, L.; Chen, P.; Meltzer, P.; Small, D. Constitutive Fms-like tyrosine kinase 3 activation results in specific changes in gene expression in myeloid leukaemic cells. Br J Haematol. 2007 Sep;138(5):603-615.
Li, L.; Piloto, O.; Kim, K.T.; Ye, Z.; Nguyen, H.B.; Yu, X.; Levis, M.; Cheng, L.; Small, D. FLT3/ITD expression increases expansion, survival and entry into cell cycle of human haematopoietic stem/progenitor cells. Br J Haematol. 2007 Apr;137(1):64-75.
Piloto, O.; Wright, M.; Brown, P.; Kim, K.T.; Levis, M.; Small, D. Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways. Blood. 2007 Feb 15;109(4):1643-1652.
Li, L.; Piloto, O.; Nguyen, H.B.; Greenberg, K.; Takamiya, K.; Racke, F.; Huso, D.; Small, D. Knock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model. Blood. 2008 Apr 1;111(7):3849-3858.
Sallmyr, A.; Fan, J.; Datta, K.; Kim, K.T.; Grosu, D.; Shapiro, P.; Small, D.; Rassool, F. Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage and misrepair: implications for poor prognosis in AML. Blood. 2008 Jan 11.
Small, D. Targeting FLT3 for the treatment of leukemia. Seminars in hematology. 2008 Jul;45(3 Suppl 2):S17-21.
Whartenby, K.A.; Small, D.; Calabresi, P.A. FLT3 inhibitors for the treatment of autoimmune disease. Expert Opin Investig Drugs. 2008 Nov;17(11):1685-1692.
Pratz, K.W.; Cortes, J.; Roboz, G.J.; Rao, N.; Arowojolu, O.; Stine, A.; Shiotsu, Y.; Shudo, A.; Akinaga, S.; Small, D.; Karp, J.E.; Levis, M. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009 Apr 23;113(17):3938-3946.
Schafer, E.; Irizarry, R.; Negi, S.; McIntyre, E.; Small, D.; Figueroa, M.E.; Melnick, A.; Brown, P. Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting. Blood. 2010 Jun 10;115(23):4798-4809.
Locations
- The Johns Hopkins Hospital
- 1800 Orleans Street, Baltimore, MD 21287
- phone: 410-955-5000
- fax: 410-955-5001
Expertise
Education
Johns Hopkins University School of Medicine
Fellowship, 1990Johns Hopkins University School of Medicine
Residency, Pediatrics, 1987Johns Hopkins University School of Medicine
Medical Education, MD, 1985Insurance
- Aetna
- CareFirst
- Cigna
- First Health
- Geisinger Health Plan
- HealthSmart/Accel
- Humana
- Johns Hopkins Health Plans
- MultiPlan
- Pennsylvania's Preferred Health Networks (PPHN)
- Point Comfort Underwriters
- Private Healthcare Systems (PHCS)
- UnitedHealthcare
- Veteran Affairs Community Care Network (Optum-VACCN)