CURRENT CLINICAL INTERESTS
Acute leukemia, myelodysplastic syndrome, multiple myeloma, stem cell transplant
CURRENT RESEARCH INTERESTS
Cell adhesion mediated chemotherapy resistance in acute myeloid leukemia and multiple myeloma, personalized leukemia therapy, hematopoietic stem cell gene transfer for Fanconi anemia
Dr. Becker is pursuing several areas of research investigation, including 1) the mechanism of adhesion mediated chemotherapy resistance in acute myeloid leukemia and 2) hematopoietic stem cell gene therapy for an inherited disorder of DNA repair, Fanconi anemia.
1. Optimizing therapy of hematological malignancies.
a. Environment mediated chemotherapy resistance in acute myeloid leukemia (AML) and multiple myeloma.
We have performed extensive analysis of the interaction of acute myeloid leukemia or multiple myeloma with the bone marrow microenvironment, focusing on receptors such as VLA-4, CXCR-4 and CD44/E-selectin ligand. We test novel combinations of chemotherapy with agents that disrupt adhesion of leukemia or myeloma cells in the laboratory, with the goal of development of new clinical trials in patients.
b. Personalized therapy of AML.
Our goal is to better predict outcomes in AML based on in vitro high throughput drug sensitivity assays in combination with genomic information and gene expression, and develop new treatments for AML with novel targeted agents.
2. Gene therapy for inherited stem cell disorders.
We performed the preclinical studies with a lentiviral vector in support of a gene therapy clinical trial for Fanconi (aplastic) anemia that is currently open for enrollment.
Becker PS, Li Z, Potselueva T, Madri JA,
Newburger PE. Berliner N. Laminin promotes differentiation of NB4
promyelocytic leukemia cells with all-trans retinoic acid. Blood 88:261-267, 1996.
Rossi H, O'Donnell J, Sarcinelli F, Stewart FM,
Quesenberry PJ, Becker PS. GM-CSF priming with successive concomitant
therapy with low dose Ara-C for elderly patients with secondary/refractory
acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia
Nowakowski GS, Dooner MS, Valinski HM, Mihaliak
AM, Quesenberry PJ, and Becker PS. A specific heptapeptide from a phage display
peptide library homes to bone marrow and binds to primitive hematopoietic stem
cells. Stem Cells 22:1030-1038, 2004.
Gold J, Valinski, HM, Hanks AN, Ballen KK, Hsieh CC,
Becker PS. Adhesion receptor expression by CD34+ cells from peripheral blood or bone marrow grafts: correlation with time to engraftment. Exp.
Hematol. 34(5):680-7, 2006.
Becker PS, Kopecky KJ, Wilks AN, Chien S, Harlan JM, Willman CL, Petersdorf SH, Stirewalt DL, Papayannopoulou T, Appelbaum FR. Very late antigen-4 (VLA-4) function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia. Blood 113:866-874, 2009.
Rosenbloom B, Becker P, Weinreb N. Multiple myeloma and Gaucher genes. Genet. Med., 11:134, 2009.
Becker PS, Taylor JA, Trobridge GD, Zhao X, Beard BC, Chien S, Adair J, Kohn DB, Wagner JE, Shimamura A and Kiem H-P. Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector. Gene Therapy 17:1244-1252, 2010.
Becker PS. Genetic predisposition for chemotherapy induced neuropathy in multiple myeloma. J. Clin. Oncol. 29:783-786, 2011.
Becker PS, Kantarjian HM,
Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukemia. Brit. J. Haematol. 155:182-189, 2011.
Becker PS. Dependence of acute myeloid leukemia on adhesion within the bone marrow microenvironment. Scientific World JOURNAL, 2012:856467, 2012.
Miller CP, Rattray K, Zhang Y, Wood BL, Burwick N, Chien S, Bensinger WI, Blau CA, Becker PS. Evaluating surface erythropoietin receptor in multiple myeloma. Leukemia 26:1883-6, 2012.
Adair J, Zhao X, Chien S, Fang M, Wohlfahrt ME, Trobridge G, Taylor J, Beard BC, Kiem H-P, Becker PS. Conditioning regimens for gene transfer for Fanconi Anemia. J Mol Med 90:1283-94, 2012
Becker PS, Kantarjian HM, Appelbaum FR, Storer B, Pierce S, Shan J, Faderl S, Estey EH. Retrospective comparison of clofarabine versus fludarabine in combination with high dose cytarabine with or without G-CSF as salvage therapies for acute myeloid leukemia (AML). Haematologica 98:114-8, 2013.
Roshal M, Chien S, Othus M, Wood B, Fang M, Appelbaum FR, Estey EH, Papayannopoulou T, and Becker PS. The proportion of CD34+CD38low or neg myeloblasts, but not side population (SP) frequency, predicts initial response to induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Leukemia 27:728-31, 2013.
Bensinger WI, Green DJ, Burwick N, Becker PS. A prospective study of lenalidomide monotherapy for relapse after Allo-SCT for multiple myeloma. Bone Marrow Transplant. 2014 Apr;49(4):492-5.
Weiss MD, Becker P. Paradoxical worsening of anti–myelin-associated glycoprotein polyneuropathy following rituximab. Muscle Nerve. 2014 Mar;49(3):457-8.
Becker PS. Optimizing stem cell mobilization: Lessons learned. J Natl Compr Canc Netw. 2014 Oct;12(10):1443-9.
Huang JC, Basu SK, Zhao X, Chien S, Fang M, Oehler V, Appelbaum FR, Becker PS. Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration. Blood Cancer Journal. 5:e302, 2015.
Becker PS, Medeiros BC, Stein AS, Othus M, Appelbaum FR, Forman SJ, Scott BL, Hendrie PC, Gardner KM, Pagel JM, Walter RB, Parks C, Wood BL, Abkowitz JL,, Estey EH. G-CSF priming, clofarabine, and high doce cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol. 90(4):295-300, 2015.
Scott BL, Becker PS. JAK/STAT Pathway Inhibitors and Neurologic Toxicity Above All Else Do No Harm?. JAMA Oncol. 1:651-2, 2015.
Becker PS, Gooley TA, Green DJ, Burwick N, Kim TY, Kojouri K, Inoue Y, Moore DJ, Nelli E, Denni T, Bensinger WI. A phase 2 study of bortezomib, cyclophosphamide, pegylated liposomal doxorubicin and dexamethasone (BCDD) for newly diagnosed multiple myeloma. Blood Cancer Journal. 6:e422; 2016.