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Harry A Drabkin, MD
Professor of Medicine
Hematology/Oncology
College of Medicine
MUSC

Email: drabkin@musc.edu
 
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Harry A Drabkin, MD

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Research Interest:

I have made important contributions to cancer cell biology in the areas of acute leukemia, kidney cancer and lung cancer. I discovered the AML1/RUNX1 - ETO fusion in the acute myelogenous leukemia 8;21 translocation and the hereditary kidney cancer gene, TRC8, subsequently elucidating its function as an E3-ubiquitin ligase targeting the pre-SREBP transcription factors that regulate cholesterol biosynthesis. In lung cancer, I discovered the secreted semaphorin, SEMA3F, and found that it functions as a potent tumor suppressor frequently deleted or downregulated in this disease. I am also known for my work on EMT in lung cancer and the role of ZEB1 in this process. Clinically, I am recognized in the treatment of metastatic kidney cancer and am active in cooperative groups, industry, and investigator-initiated clinical trials.

Honors:
Gilbreth Chair in Clinical Oncology, Hollings Cancer Center, Medical University of South Carolina

Positions:
Chief, Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina

Selected Publications:

1.Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, Vaishampayan UN, Drabkin HA, George S, Logan TF, Margolin KA, Plimack ER, Lambert AM, Waxman IM, Hammers HJ. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol. ., 2014.
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2.Nasarre P, Gemmill RM, Drabkin HA. The emerging role of class-3 semaphorins and their neuropilin receptors in oncology. Onco Targets Ther. .7:1663-87, 2014. PMCID: PMC4181631
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3.Kato T, Franconi CP, Sheridan MB, Hacker AM, Inagakai H, Glover TW, Arlt MF, Drabkin HA, Gemmill RM, Kurahashi H, Emanuel BS. Analysis of the t(3;8) of hereditary renal cell carcinoma: a palindrome-mediated translocation. Cancer Genet. .207(4):133-40, 2014. PMCID: PMC4102306
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4.Rosenberg JE, Bambury RM, Van Allen EM, Drabkin HA, Lara PN, Harzstark AL, Wagle N, Figlin RA, Smith GW, Garraway LA, Choueiri T, Erlandsson F, Laber DA. A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma. Invest New Drugs. .32(1):178-87, 2013.
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5.Nasarre P, Gemmill RM, Potiron VA, Roche J, Lu X, Barón AE, Korch C, Garrett-Mayer E, Lagana A, Howe PH, Drabkin HA. Neuropilin-2 Is upregulated in lung cancer cells during TGF-ß1-induced epithelial-mesenchymal transition. Cancer Res. .73(23):7111-21, 2013. PMCID: PMC3926507
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6.Chakravarty S, Lai WC, Zou Y, Drabkin HA, Gemmill RM, Simon GR, Chin SH, Chen RT. Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors. Biosens Bioelectron. .43:50-5, 2012. PMCID: PMC3594323
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7.Drabkin HA, Gemmill RM. Cholesterol and the development of clear-cell renal carcinoma. Curr Opin Pharmacol. .12(6):742-50, 2012.
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8.Dasari A, Gore L, Messersmith WA, Diab S, Jimeno A, Weekes CD, Lewis KD, Drabkin HA, Flaig TW, Camidge DR. A phase I study of sorafenib and vorinostat in patients with advanced solid tumors with expanded cohorts in renal cell carcinoma and non-small cell lung cancer. Invest New Drugs. .31(1):115-25, 2012.
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9.Millward M, Price T, Townsend A, Sweeney C, Spencer A, Sukumaran S, Longenecker A, Lee L, Lay A, Sharma G, Gemmill RM, Drabkin HA, Lloyd GK, Neuteboom ST, McConkey DJ, Palladino MA, Spear MA. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Invest New Drugs. .30(6):2303-17, 2011.
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10.Petit A, Ragu C, Soler G, Ottolenghi C, Schluth C, Radford-Weiss I, Schneider-Maunoury S, Callebaut I, Dastugue N, Drabkin HA, Bernard OA, Romana S, Penard-Lacronique V. Functional analysis of the NUP98-CCDC28A fusion protein. Haematologica. .97(3):379-87, 2011. PMCID: PMC3291592
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11.Starkova J, Gadgil S, Qiu YH, Zhang N, Hermanova I, Kornblau SM, Drabkin HA. Up-regulation of homeodomain genes, DLX1 and DLX2, by FLT3 signaling. Haematologica. .96(6):820-8, 2011. PMCID: PMC3105643
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12.Starkova J, Zamostna B, Mejstrikova E, Krejci R, Drabkin HA, Trka J. HOX gene expression in phenotypic and genotypic subgroups and low HOXA gene expression as an adverse prognostic factor in pediatric ALL. Pediatr Blood Cancer. .55(6):1072-82, 2010.
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13.Gemmill RM, Roche J, Potiron VA, Nasarre P, Mitas M, Coldren CD, Helfrich BA, Garrett-Mayer E, Bunn PA, Drabkin HA. ZEB1-responsive genes in non-small cell lung cancer. Cancer Lett. .300(1):66-78, 2010. PMCID: PMC3337721
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14.Flaig TW, Costa LJ, Gustafson DL, Breaker K, Schultz MK, Crighton F, Kim FJ, Drabkin H. Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib. Br J Cancer. .103(6):796-801, 2010. PMCID: PMC2966634
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15.Bukowski RM, Stadler WM, McDermott DF, Dutcher JP, Knox JJ, Miller WH, Hainsworth JD, Henderson CA, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Figlin RA. Safety and efficacy of sorafenib in elderly patients treated in the North American advanced renal cell carcinoma sorafenib expanded access program. Oncology. .78(5-6):340-7, 2010.
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16.Sheridan MB, Kato T, Haldeman-Englert C, Jalali GR, Milunsky JM, Zou Y, Klaes R, Gimelli G, Gimelli S, Gemmill RM, Drabkin HA, Hacker AM, Brown J, Tomkins D, Shaikh TH, Kurahashi H, Zackai EH, Emanuel BS. A palindrome-mediated recurrent translocation with 3:1 meiotic nondisjunction: the t(8;22)(q24.13;q11.21). Am J Hum Genet. .87(2):209-18, 2010. PMCID: PMC2917714
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17.Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. .116(5):1272-80, 2010.
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18.Lee JP, Brauweiler A, Rudolph M, Hooper JE, Drabkin HA, Gemmill RM. The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways. Mol Cancer Res. .8(1):93-106, 2010. PMCID: PMC3086825
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19.Nasarre P, Potiron V, Drabkin H, Roche J. Guidance molecules in lung cancer. Cell Adh Migr. .4(1):130-45, 2010. PMCID: PMC2852570
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20.Drabkin HA, Gemmill RM. Obesity, cholesterol, and clear-cell renal cell carcinoma (RCC). Adv Cancer Res. .107:39-56, 2010.
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21.Roche J, Drabkin H. Letter from the guest editors. Cell Adh Migr. .4(1):94-5, 2010. PMCID: PMC2852564
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22.Kakihana M, Ohira T, Chan D, Webster RB, Kato H, Drabkin HA, Gemmill RM. Induction of E-cadherin in lung cancer and interaction with growth suppression by histone deacetylase inhibition. J Thorac Oncol. .4(12):1455-65, 2009. PMCID: PMC2796578
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23.Konoplev S, Huang X, Drabkin HA, Koeppen H, Jones D, Kantarjian HM, Garcia-Manero G, Chen W, Medeiros LJ, Bueso-Ramos CE. Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis. Cancer. .115(20):4737-44, 2009. PMCID: PMC4199225
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24.Stagg HR, Thomas M, van den Boomen D, Wiertz EJ, Drabkin HA, Gemmill RM, Lehner PJ. The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER. J Cell Biol. .186(5):685-92, 2009. PMCID: PMC2742190
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25.Gimelli S, Beri S, Drabkin HA, Gambini C, Gregorio A, Fiorio P, Zuffardi O, Gemmill RM, Giorda R, Gimelli G. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma. Mol Cancer. .8:52, 2009. PMCID: PMC2727492
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26.Arighi CN, Liu H, Natale DA, Barker WC, Drabkin H, Blake JA, Smith B, Wu CH. TGF-beta signaling proteins and the Protein Ontology. BMC Bioinformatics. .10 Suppl 5:S3, 2009. PMCID: PMC2679403
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27.Cappuzzo F, Varella-Garcia M, Rossi E, Gajapathy S, Valente M, Drabkin H, Gemmill R. MYC and EIF3H Coamplification significantly improve response and survival of non-small cell lung cancer patients (NSCLC) treated with gefitinib. J Thorac Oncol. .4(4):472-8, 2009. PMCID: PMC2774779
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28.Miura N, Sato R, Tsukamoto T, Shimizu M, Kabashima H, Takeda M, Takahashi S, Harada T, West JE, Drabkin H, Mejia JE, Shiota G, Murawaki Y, Virmani A, Gazdar AF, Oshimura M, Hasegawa J. A noncoding RNA gene on chromosome 10p15.3 may function upstream of hTERT. BMC Mol Biol. .10:5, 2009. PMCID: PMC2661890
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29.Clarhaut J, Gemmill RM, Potiron VA, Ait-Si-Ali S, Imbert J, Drabkin HA, Roche J. ZEB-1, a repressor of the semaphorin 3F tumor suppressor gene in lung cancer cells. Neoplasia. .11(2):157-66, 2009. PMCID: PMC2631140
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30.Andreeff M, Ruvolo V, Gadgil S, Zeng C, Coombes K, Chen W, Kornblau S, Barón AE, Drabkin HA. HOX expression patterns identify a common signature for favorable AML. Leukemia. .22(11):2041-7, 2008. PMCID: PMC2676170
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31.Potiron VA, Roche J, Drabkin HA. Semaphorins and their receptors in lung cancer. Cancer Lett. .273(1):1-14, 2008. PMCID: PMC2630718
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32.Ballonoff A, Kavanagh B, Nash R, Drabkin H, Trotter J, Costa L, Rabinovitch R. Hodgkin lymphoma-related vanishing bile duct syndrome and idiopathic cholestasis: statistical analysis of all published cases and literature review. Acta Oncol. .47(5):962-70, 2008.
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33.Costa LJ, Drabkin HA. Renal cell carcinoma: new developments in molecular biology and potential for targeted therapies. Oncologist. .12(12):1404-15, 2007.
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34.Baselga J, Tabernero J. Combined antiangiogenesis and antiepidermal growth factor receptor targeting in the treatment of cancer: hold back, we are not there yet. J Clin Oncol. .25(29):4516-8, 2007.
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35.Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. .25(29):4536-41, 2007.
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36.Potiron VA, Sharma G, Nasarre P, Clarhaut JA, Augustin HG, Gemmill RM, Roche J, Drabkin HA. Semaphorin SEMA3F affects multiple signaling pathways in lung cancer cells. Cancer Res. .67(18):8708-15, 2007.
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37.Poland KS, Azim M, Folsom M, Goldfarb R, Naeem R, Korch C, Drabkin HA, Gemmill RM, Plon SE. A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption of the TRC8 gene and predisposition to clear cell renal cell carcinoma. Genes Chromosomes Cancer. .46(9):805-12, 2007.
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38.Ryan CW, Goldman BH, Lara PN, Mack PC, Beer TM, Tangen CM, Lemmon D, Pan CX, Drabkin HA, Crawford ED. Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol. .25(22):3296-301, 2007.
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39.Costa LJ, Gemmill RM, Drabkin HA. Upstream signaling inhibition enhances rapamycin effect on growth of kidney cancer cells. Urology. .69(3):596-602, 2007.
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40.Brauweiler A, Lorick KL, Lee JP, Tsai YC, Chan D, Weissman AM, Drabkin HA, Gemmill RM. RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary kidney cancer gene. Oncogene. .26(16):2263-71, 2006.
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41.Xavier AC, Marshall C, La Rosa FG, Costa LJ, Drabkin H, Crawford ED. Woman with a papillary pulmonary lesion and a complex renal cyst. Oncology (Williston Park). .20(11):1437-9, 1443, 2006.
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42.Su X, Drabkin H, Clappier E, Morgado E, Busson M, Romana S, Soulier J, Berger R, Bernard OA, Lavau C. Transforming potential of the T-cell acute lymphoblastic leukemia-associated homeobox genes HOXA13, TLX1, and TLX3. Genes Chromosomes Cancer. .45(9):846-55, 2006.
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43.Dohadwala M, Yang SC, Luo J, Sharma S, Batra RK, Huang M, Lin Y, Goodglick L, Krysan K, Fishbein MC, Hong L, Lai C, Cameron RB, Gemmill RM, Drabkin HA, Dubinett SM. Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E(2) induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer. Cancer Res. .66(10):5338-45, 2006.
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44.Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L, Helfrich B, Dziadziuszko R, Chan DC, Sugita M, Chan Z, Baron A, Franklin W, Drabkin HA, Girard L, Gazdar AF, Minna JD, Bunn PA. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res. .66(2):944-50, 2006.
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45.Gemmill RM, Zhou M, Costa L, Korch C, Bukowski RM, Drabkin HA. Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma. Br J Cancer. .92(12):2266-77, 2005. PMCID: PMC2361810
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46.Gemmill RM, Lee JP, Chamovitz DA, Segal D, Hooper JE, Drabkin HA. Growth suppression induced by the TRC8 hereditary kidney cancer gene is dependent upon JAB1/CSN5. Oncogene. .24(21):3503-11, 2005.
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47.Kusy S, Nasarre P, Chan D, Potiron V, Meyronet D, Gemmill RM, Constantin B, Drabkin HA, Roche J. Selective suppression of in vivo tumorigenicity by semaphorin SEMA3F in lung cancer cells. Neoplasia. .7(5):457-65, 2005. PMCID: PMC1501157
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48.Nasarre P, Kusy S, Constantin B, Castellani V, Drabkin HA, Bagnard D, Roche J. Semaphorin SEMA3F has a repulsing activity on breast cancer cells and inhibits E-cadherin-mediated cell adhesion. Neoplasia. .7(2):180-9, 2005. PMCID: PMC1501131
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49.Roche J, Zeng C, Barón A, Gadgil S, Gemmill RM, Tigaud I, Thomas X, Drabkin HA. Hox expression in AML identifies a distinct subset of patients with intermediate cytogenetics. Leukemia. .18(6):1059-63, 2004.
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50.Ohira T, Gemmill RM, Ferguson K, Kusy S, Roche J, Brambilla E, Zeng C, Baron A, Bemis L, Erickson P, Wilder E, Rustgi A, Kitajewski J, Gabrielson E, Bremnes R, Franklin W, Drabkin HA. WNT7a induces E-cadherin in lung cancer cells. Proc Natl Acad Sci U S A. .100(18):10429-34, 2003. PMCID: PMC193578
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51.Nasarre P, Constantin B, Rouhaud L, Harnois T, Raymond G, Drabkin HA, Bourmeyster N, Roche J. Semaphorin SEMA3F and VEGF have opposing effects on cell attachment and spreading. Neoplasia. .5(1):83-92, 2003. PMCID: PMC1502125
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52.de Guzman CG, Warren AJ, Zhang Z, Gartland L, Erickson P, Drabkin H, Hiebert SW, Klug CA. Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol Cell Biol. .22(15):5506-17, 2002. PMCID: PMC133929
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53.Gemmill RM, Bemis LT, Lee JP, Sozen MA, Baron A, Zeng C, Erickson PF, Hooper JE, Drabkin HA. The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway. Oncogene. .21(22):3507-16, 2002.
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54.Bremnes RM, Veve R, Gabrielson E, Hirsch FR, Baron A, Bemis L, Gemmill RM, Drabkin HA, Franklin WA. High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol. .20(10):2417-28, 2002.
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55.Drabkin HA, Parsy C, Ferguson K, Guilhot F, Lacotte L, Roy L, Zeng C, Baron A, Hunger SP, Varella-Garcia M, Gemmill R, Brizard F, Brizard A, Roche J. Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia. Leukemia. .16(2):186-95, 2002.
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56.Tomizawa Y, Sekido Y, Kondo M, Gao B, Yokota J, Roche J, Drabkin H, Lerman MI, Gazdar AF, Minna JD. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci U S A. .98(24):13954-9, 2001. PMCID: PMC61148
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57.Varella-Garcia M, Hogan CJ, Odom LF, Murata-Collins JL, Ai H, Chen L, Richkind K, Paskulin G, Andreeff M, Brizard A, McGavran L, Gemmill RM, Berger R, Drabkin HA. Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting. Leukemia. .15(9):1408-14, 2001.
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58.Ueda M, Gemmill RM, West J, Winn R, Sugita M, Tanaka N, Ueki M, Drabkin HA. Mutations of the beta- and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas. Br J Cancer. .85(1):64-8, 2001. PMCID: PMC2363927
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59.Calvo R, West J, Franklin W, Erickson P, Bemis L, Li E, Helfrich B, Bunn P, Roche J, Brambilla E, Rosell R, Gemmill RM, Drabkin HA. Altered HOX and WNT7A expression in human lung cancer. Proc Natl Acad Sci U S A. .97(23):12776-81, 2000. PMCID: PMC18840
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60.Brambilla E, Constantin B, Drabkin H, Roche J. Semaphorin SEMA3F localization in malignant human lung and cell lines: A suggested role in cell adhesion and cell migration. Am J Pathol. .156(3):939-50, 2000. PMCID: PMC1876858
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61.Drabkin HA, West JD, Hotfilder M, Heng YM, Erickson P, Calvo R, Dalmau J, Gemmill RM, Sablitzky F. DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC. Oncogene. .18(16):2589-97, 1999.
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62.Gemmill RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, Li F, Drabkin HA. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc Natl Acad Sci U S A. .95(16):9572-7, 1998. PMCID: PMC21380
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63.Paskulin GA, Philips G, Morgan R, Sandberg A, Richkind K, Borovik C, McGavran L, Rabinovich N, Dietz-Band J, Erickson P, Drabkin H, Varella-Garcia M. Pre-clinical evaluation of probes to detect t(8;21) AML minimal residual disease by fluorescence in situ hybridization. Genes Chromosomes Cancer. .21(2):144-51, 1998.
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64.David G, Abbas N, Stevanin G, Dürr A, Yvert G, Cancel G, Weber C, Imbert G, Saudou F, Antoniou E, Drabkin H, Gemmill R, Giunti P, Benomar A, Wood N, Ruberg M, Agid Y, Mandel JL, Brice A. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet. .17(1):65-70, 1997.
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65.Boldog F, Gemmill RM, West J, Robinson M, Robinson L, Li E, Roche J, Todd S, Waggoner B, Lundstrom R, Jacobson J, Mullokandov MR, Klinger H, Drabkin HA. Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B. Hum Mol Genet. .6(2):193-203, 1997.
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66.Erickson PF, Dessev G, Lasher RS, Philips G, Robinson M, Drabkin HA. ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease. Blood. .88(5):1813-23, 1996.
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67.Roche J, Boldog F, Robinson M, Robinson L, Varella-Garcia M, Swanton M, Waggoner B, Fishel R, Franklin W, Gemmill R, Drabkin H. Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin. Oncogene. .12(6):1289-97, 1996.
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68.Erickson PF, Robinson M, Owens G, Drabkin HA. The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor. Cancer Res. .54(7):1782-6, 1994.
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69.Boldog FL, Gemmill RM, Wilke CM, Glover TW, Nilsson AS, Chandrasekharappa SC, Brown RS, Li FP, Drabkin HA. Positional cloning of the hereditary renal carcinoma 3;8 chromosome translocation breakpoint. Proc Natl Acad Sci U S A. .90(18):8509-13, 1993. PMCID: PMC47386
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70.Nucifora G, Begy CR, Erickson P, Drabkin HA, Rowley JD. The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc Natl Acad Sci U S A. .90(16):7784-8, 1993. PMCID: PMC47227
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71.Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood. .80(7):1825-31, 1992.
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