Dr. Borowitz's research focuses on defining the complexity of hematologic neoplasms. He is particularly interested in the immunologic aspects of leukemia and lymphoma, and in the relation of phenotypic variability to clinical and biological heterogeneity in these diseases. He employs routine morphologic techniques and immunocytochemistry in his investigations, but he is particularly interested in flow cytometry. A major focus of his efforts has been in childhood acute lymphocytic leukemia, in conjunction with investigators in the Children's Oncology Group. He is specifically interested in studies of minimal residual disease (MRD) as detected by flow cytometry and its effect on prognosis. He is also interested in developing new clinical applications of flow cytometry, particularly as it applies to blood and bone marrow.
Over the past five years, Dr. Borowitz's lab has studied samples of more than 2,000 patients enrolled in Children's Oncology Group trials from more than 100 institutions, and has demonstrated that nearly 30 percent of them harbor MRD at the end of induction therapy. MRD at the end of induction therapy was shown to correlate with early marrow response as assessed by day 7 marrow morphology, thereby validating the assumption that this is an additional means to assess response to therapy. MRD correlates with other risk factors, including age, white count and cytogenetic abnormalities, but any subgroup of patients defined by traditional risk factors can be divided into MRD-positive and MRD-negative groups; some good-risk groups have paradoxically high levels of MRD at end induction, suggesting that the pattern of response to therapy may be dependent on specific genetic abnormalities. Data on the correlation of MRD with patient outcome are still maturing.
Neoplastic Hematopathology & Flow Cytometry
- Horton TM, Sposto R, Brown P, Reynolds CP, Hunger SP, Winick NJ, Raetz EA, Carroll WL, Arceci RJ, Borowitz MJ, Gaynon PS, Gore L, Jeha S, Maurer BJ, Siegel SE, Biondi A, Kearns PR, Narendran A, Silverman LB, Smith MA, Zwaan CM, Whitlock JA; ALLNA 2008 Conference. "Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference." Pediatr Blood Cancer. 2010 Jul 1;54(7):872-8. doi: 10.1002/pbc.22414.
- Gutierrez A, Sanda T, Ma W, Zhang J, Grebliunaite R, Dahlberg S, Neuberg D, Protopopov A, Winter SS, Larson RS, Borowitz MJ, Silverman LB, Chin L, Hunger SP, Jamieson C, Sallan SE, Look AT. "Inactivation of LEF1 in T-cell acute lymphoblastic leukemia." Blood. 2010 Apr 8;115(14):2845-51. doi: 10.1182/blood-2009-07-234377. Epub 2010 Feb 1.
- Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR, Wittwer CT, Richards SJ; Clinical Cytometry Society. "Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry." Cytometry B Clin Cytom. 2010 Jul;78(4):211-30. doi: 10.1002/cyto.b.20525.
- Gutierrez A, Dahlberg SE, Neuberg DS, Zhang J, Grebliunaite R, Sanda T, Protopopov A, Tosello V, Kutok J, Larson RS, Borowitz MJ, Loh ML, Ferrando AA, Winter SS, Mullighan CG, Silverman LB, Chin L, Hunger SP, Sallan SE, Look AT. "Absence of biallelic TCRgamma deletion predicts early treatment failure in pediatric T-cell acute lymphoblastic leukemia." J Clin Oncol. 2010 Aug 20;28(24):3816-23. doi: 10.1200/JCO.2010.28.3390. Epub 2010 Jul 19.
- Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ, Chen IM, Atlas SR, Kang H, Ar K, Wilson CS, Wharton W, Murphy M, Devidas M, Carroll AJ, Borowitz MJ, Bowman WP, Downing JR, Relling M, Yang J, Bhojwani D, Carroll WL, Camitta B, Reaman GH, Smith M, Hunger SP, Willman CL. "Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome." Blood. 2010 Dec 2;116(23):4874-84. doi: 10.1182/blood-2009-08-239681. Epub 2010 Aug 10.
Borowitz MJ, Pullen DJ, Shuster JJ, Viswanatha D, Montgomery K, Willman CL, Camitta B. (2003) Minimal residual disease detection in childhood precursorB-cell acute lymphoblastic leukemia: Relation to other risk factors. A Childrens Oncology Group Study Leukemia 17:1566-1572
Weir EG, Cowan K, LeBeau P, Borowitz MJ. (1999) A limited antibody panel can distinguish B-precursor acute lymphoblastic leukemia from normal B-precursors with four color flow cytometry: implications for residual disease detection. Leukemia 13:558-567.
Nicol TL, Silberman M, Rosenthal DL, Borowitz MJ. (2000) The accuracy of combined cytopathologic and flow cytometric analysis of fine-needleaspirates of lymph nodes. Am J Clin Pathol; 114:18-28.
Brodsky RA, Mukhina GL, Li S, Nelson KL, Chiurazzi PL, Buckley JT, Borowitz MJ. (2000) Improved detection and characterization of paroxysmalnocturnal hemoglobinuria using fluorescent aerolysin. AM J Clin Pathol 114:459-466.