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Biosketch / Results /

David J. Araten, M.D.

Assistant Professor;
Department of Medicine (Hematology Div) [1]
NYU Hematology Associates

Clinical Addresses

240 EAST 38TH STREET
19TH FLOOR
NEW YORK, NY 10016
Phone: 212-731-5186
[3]

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Medical Specialties

Cancer, Hematology

Medical Expertise

Hematologic Cancer, Anemia

Clinical Responsibilities

Dr. Araten's areas of interest within the field of Hematology include the care of patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) and Aplastic Anemia. Dr. Araten holds regular office hours at the NYU Clinical Cancer Center.

Insurance

AETNA HMO, AETNA INDEMNITY, AETNA MEDICARE, AETNA POS, AETNA PPO, AFFINITY, Cigna HMO/POS, Cigna PPO, EBCBS EPO, EBCBS HLTHY NY, EBCBS HMO, EBCBS INDEMNITY, EBCBS MEDIBLUE, EBCBS POS, EBCBS PPO, GHI CBP, HIP ACCESS I, HIP ACCESS II, HIP CHLD HLTH, HIP EPO/PPO, HIP FAM HLTH, HIP HMO, HIP MEDICAID, HIP MEDICARE, HIP POS, LOCAL 1199 PPO, MAGNACARE PPO, MULTIPLAN/PHCS PPO, Medicare, NY MEDICAID, OXFORD FREEDOM, Oxford Liberty, Oxford Medicare, UHC COMMUNITY & STATE PLAN, UHC EPO, UHC HMO, UHC MEDICARE, UHC POS, UHC PPO, UHC TOP TIER, UPN Elite

Insurance Disclaimer: Insurance listed above may not be accepted at all office locations. Please confirm prior to each visit. The information presented here may not be complete or may have changed.

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Board Certification

1998 — Ab Internal Medicine (Hematology)
1998 — Ab Internal Medicine (Medical Oncology)
2004 — Ab Internal Medicine - Internal Medicine

Education

1991 — Harvard Medical School, Medical Education
1991-1994 — Columbia-Presbyterian Medical Center (Internal Medicine), Residency Training
1991-1994 — Columbia-Presbyterian Medical Center (Internal Medicine), Internship
1994-1999 — Memorial Sloan-Kettering Cancer Center (Hematology Oncology), Clinical Fellowships

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Research Summary

Acquired inactivating somatic mutations are likely to be critical in the development of malignancies, and yet they are extremely difficult to detect in populations of normal human cells. This is because mutations are rare, and most mutations will either not produce a phenotype, or conversely, will interfere with the survival of the cell. Furthermore, because of the diploid nature of the human genome, the effect of inactivating mutations would tend to be complemented by the wild type allele on the homologous chromosome. One way around this problem is to study genes that are on the X-chromosome, which is present in only one copy in cells from males and which is present in only one functional copy in cells from females, due to Lyonization. Historically, the identification of rare mutants has been possible for the X-linked HPRT gene; inactivating mutations in this gene allow for the cell to grow in the presence of 6-thioguanine. It has been known for some time that normal individuals harbor circulating 6-thioguanine-resistant lymphocytes that arise due to acquired HPRT mutations, and these can be enumerated by limiting dilution cloning. Our laboratory uses two different X-linked genes, PIG-A and XK, as sentinels for spontaneous somatic mutations. These genes have the advantage that the mutant phenotype affects surface proteins, so that the mutants can be picked up by flow cytometry using monoclonal antibodies, which can rapidly screen for rare mutants within a population of over a million cells within minutes. PIG-A is the gene that is mutated in the condition Paroxysmal Nocturnal Hemoglobinuria (PNH) and it is known that a broad spectrum of mutations can confer the PIG-A null phenotype. It is thought that apart from the very special case of PNH, PIG-A mutants have neither a growth advantage or disadvantage. PIG-A encodes an enzyme that is essential in the biosynthesis of the structure glycosylphosphatidylinositol (GPI). A subset of proteins lack transmembrane domains and require the GPI structure for their association with the cell surface. Because of the central role of PIG-A in the synthesis of GPI, when this gene is mutated, the expression of all GPI-linked proteins is affected, and antibodies specific for more than one GPI-linked protein can be used simultaneously to increase the specificity of the assay. Similarly, the FLAER reagent binds to GPI directly and can be used for the same purpose. The expression of transmembrane proteins is not affected by the mutation in PIG-A, and antibodies recognizing a lineage specific marker that does not depend upon GPI is useful to identify intact cells.

Research Interests

We have found that using flow cytometry to detect the GPI-negative phenotype, it is possible to measure the frequency of spontaneous mutants within populations of hematopoietic cells of different lineages from normal individuals, without the requirement for cell growth. For cells that do grow well, we have also found that it is possible to eliminate pre-existing mutants from a population by sorting, allowing us to expand a purified GPI (+) population in vitro, so that we can calculate the rate of new mutations as they occur prospectively in a dividing population. This value, the mutation rate, is otherwise very difficult to measure in human cells, though it was first calculated by Luria and Delbruck for bacteria in the 1940's. We have been able to calculate the mutation rate in B-lymphoblastoid cell lines (BLCLs) from normal individuals, in BLCLs from patients with various genetic diseases, in expanding T cell cultures from normal individuals, in cord blood-derived CD34 cells growing under the influence of myeloid-inducing cytokines and fusion oncoproteins, as well as in cell lines derived from human hematopoietic malignancies. The XK gene is centromeric to PIG-A on the short arm of the X-chromosome and is also known to us through clinical Hematology, this being the gene that, when mutated, is responsible for the McLeod syndrome. This disorder is characterized by a great reduction in the level of Kell proteins on the surface of the red cell, probably because the XK gene product is normally covalently linked to the Kell protein through a disulfide bond. Like PIG-A, a broad spectrum of mutations are known to inactivate the gene. Obligate female heterozygotes have two populations of red cells, due to inactivation of the X-chromosome carrying either the wild type or the mutant allele. In collaboration with investigators at the New York Blood Center, we have found that normal individuals also harbor small populations of spontaneously arising Kell-low red cells that appear similar to Kell-low red cells are due to inherited mutations of XK. The laboratory is interested in using these techniques for the quantitation of rare mutations in order to predict cancer risk, to screen for compounds that might decrease the mutation rate, to study the pathophysiology of genetic cancer predisposition and premature ageing syndromes, to investigate the relationship between cancer and normal ageing, and to investigate whether an increase in the mutation rate is a requirement for carcinogenesis (as has been proposed by others). Our recent work has shown that there are two subgroups of samples of acute lymphoblastic leukemia--those with a low frequency and those with an elevation in the frequency of mutants, and we are interested in investigating the clinical significance of this phenotype. Addresses of published articles and abstracts (copy and paste into browser window): http://www.ncbi.nlm.nih.gov/pubmed/19909712?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=2 http://www.pnas.org/content/96/9/5209.full?sid=8c8f4f16-3b23-42b1-b362-ed267a8de540 http://cancerres.aacrjournals.org/cgi/content/abstract/65/18/8111 http://bloodjournal.hematologylibrary.org/cgi/content/full/108/2/734 http://ash.confex.com/ash/2008/webprogram/Paper7892.html http://www.abstracts2view.com/hem07/view.php?nu=HEM07L1_2675&terms

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search [9]

Identification of ex vivo myeloma cells with the pnh phenotype
Araten, D J; Csehak, K; Zamechek, L; Park, J; Liu, C; Ibrahim, S; Mazumder, A
2012 16 Nov 2012;:-, Blood
— id: 217012, year: 2012, vol: , page: , stat: Journal Article,

A Role for TET2 Mutations in Paroxysmal Nocturnal Hemoglobinuria (PNH)
Araten, David J.; Bains, Ashish; Lobry, Camille; Aifantis, Iannis; Ibrahim, Sherif
2012 NOV 16;120(21):-, Blood
— id: 227382, year: 2012, vol: 120, page: , stat: Journal Article,

Thrombolytic therapy is effective in paroxysmal nocturnal hemoglobinuria: a series of nine patients and a review of the literature
Araten, David J; Notaro, Rosario; Thaler, Howard T; Kernan, Nancy; Boulad, Farid; Castro-Malaspina, Hugo; Small, Trudy; Scaradavou, Andromachi; Magnan, Heather; Prockop, Susan; Chaffee, Sara; Gonsky, Jason; Thertulien, Raymond; Tarquini, Roberto; Luzzatto, Lucio
2012 Mar;97(3):344-352, Haematologica (Roma)
— id: 159828, year: 2012, vol: 97, page: 344, stat: Journal Article,

Leukemic blasts with the paroxysmal nocturnal hemoglobinuria phenotype in children with acute lymphoblastic leukemia
Araten, David J; Sanders, Katie J; Anscher, Dan; Zamechek, Leah; Hunger, Stephen P; Ibrahim, Sherif
2012 Nov;181(5):1862-1869, American journal of pathology
— id: 180502, year: 2012, vol: 181, page: 1862, stat: Journal Article,

Paroxysmal nocturnal hemoglobinuria in pediatric patients
Curran, Kevin J; Kernan, Nancy A; Prockop, Susan E; Scaradavou, Andromachi; Small, Trudy N; Kobos, Rachel; Castro-Malaspina, Hugo; Araten, David; Dimichele, Donna; O'Reilly, Richard J; Boulad, Farid
2012 Sep;59(3):525-529, Pediatric blood & cancer
— id: 174437, year: 2012, vol: 59, page: 525, stat: Journal Article,

Analysis of the mutation rate in lymphocytes derived from patients with cutaneous T-cell neoplasms using the PIG-a gene
Doratotaj, B; Zamechek, L B; Hymes, K B; Araten, D J
2012 20 May 2012;30(15):-, Journal of clinical oncology
— id: 249842, year: 2012, vol: 30, page: , stat: Journal Article,

Selective Splenic Artery Embolization for the Treatment of Thrombocytopenia and Hypersplenism in Paroxysmal Nocturnal Hemoglobinuria (PNH)
Iori, Anna Paola; Brown, Karen; Araten, David J.; Scalzulli, Emilia; Torelli, Giovanni Fernando; De Propis, Maria Stefania; Girmenia, Corrado; Salvatori, Filippo Maria; Zelig, Orly; Foa, Robin; Luzzatto, Lucio
2012 NOV 16;120(21):-, Blood
— id: 227412, year: 2012, vol: 120, page: , stat: Journal Article,

Paroxysmal nocturnal hemoglobinuria and concurrent JAK2(V617F) mutation
Sugimori, C.; Padron, E.; Caceres, G.; Shain, K.; Sokol, L.; Zhang, L.; Tiu, R.; O'Keefe, C. L.; Afable, M.; Clemente, M.; Lee, J. M.; Maciejewski, J. P.; List, A. F.; Epling-Burnette, P. K.; Araten, D. J.
2012 MAR;2:-, Blood cancer journal
— id: 166016, year: 2012, vol: 2, page: , stat: Journal Article,

Quantitative analysis of the effects of MYC overexpression on the mutation rate in human cells using the PIG-A gene
Araten, D J; Csehak, K; Anscher, D; Zamechek, L
2011 18 Nov 2011;118(21):-, Blood
— id: 169655, year: 2011, vol: 118, page: , stat: Journal Article,

Deletions of Xp22.2 including PIG-A locus lead to paroxysmal nocturnal hemoglobinuria
O'Keefe, C. L.; Sugimori, C.; Afable, M.; Clemente, M.; Shain, K.; Araten, D. J.; List, A.; Epling-Burnette, P. K.; Maciejewski, J. P.
2011 FEB ;25(2):380-+, Leukemia
— id: 127194, year: 2011, vol: 25, page: 380, stat: Journal Article,

Thrombolytic Therapy for Reversal of Thrombosis In Paroxysmal Nocturnal Hemoglobinuria (PNH)
Araten, David J.; Notaro, Rosario; Kernan, Nancy A.; Boulad, Farid; Malaspina, Hugo Castro; Small, Trudy N.; Scaradavou, Andromachi; Magnan, Heather; Prockop, Susan E.; Chaffee, Sara; Gonsky, Jason; Thertulien, Raymond; Tarquini, Roberto; Luzzatto, Lucio
2010 NOV 19 ;116(21):1721-1721, Blood
— id: 130873, year: 2010, vol: 116, page: 1721, stat: Journal Article,

The Frequency of Red Cells with a Spontaneously Appearing XK Null (McLeod like) Phenotype Is Normal In Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Araten, David J.; Zamechek, Leah; Halverson, Gregory
2010 NOV 19 ;116(21):356-357, Blood
— id: 130862, year: 2010, vol: 116, page: 356, stat: Journal Article,

A quantitative analysis of genomic instability in lymphoid and plasma cell neoplasms based on the PIG-A gene
Araten, David J; Martinez-Climent, Jose A; Perle, Mary Ann; Holm, Eliana; Zamechek, Leah; DiTata, Kimberly; Sanders, Katie J
2010 Apr 1;686(1-2):1-8, Mutation research
— id: 109511, year: 2010, vol: 686, page: 1, stat: Journal Article,

Paroxysmal Nocturnal Hemoglobinuria (PNH) In Pediatric Patients: Review of a Single Center Series
Curran, Kevin J.; Kernan, Nancy A.; Prockop, Susan E.; Scaradavou, Andromachi; Small, Trudy N.; Castro-Malaspina, Hugo; Araten, David; DiMichele, Donna; O'Reilly, Richard J.; Boulad, Farid
2010 NOV 19 ;116(21):918-918, Blood
— id: 134503, year: 2010, vol: 116, page: 918, stat: Journal Article,

Deletions of Xp22 2 Including PIG A Locus Lead to Paroxysmal Nocturnal Hemoglobinuria
Keefe, Christine L. O.; Sugimori, Chiharu; Afable, Manuel; Clemente, Michael; Shain, Kenneth; Araten, David; List, Alan F.; Burnette, P. K. Epling; Maciejewski, Jaroslaw
2010 NOV 19 ;116(21):500-500, Blood
— id: 130851, year: 2010, vol: 116, page: 500, stat: Journal Article,

The use of PIG-A as a sentinel gene for the study of the somatic mutation rate and of mutagenic agents in vivo
Peruzzi, Benedetta; Araten, David J; Notaro, Rosario; Luzzatto, Lucio
2010 Jul-Sep;705(1):3-10, Mutation research
— id: 133504, year: 2010, vol: 705, page: 3, stat: Journal Article,

A High Frequency of Blasts with the PNH Phenotype in Patients with ALL
Araten, D; Sanders, KJ; Anscher, D; Zamechek, L; Hunger, SP; Ibrahim, S
2009 NOV 20 ;114(22):630-630, Blood
— id: 109979, year: 2009, vol: 114, page: 630, stat: Journal Article,

Spontaneously arising red cells with a McLeod-like phenotype in normal donors
Araten, David J; Sanders, Katie J; Pu, Jeffrey; Lee, Soohee
2009 Dec 1;671(1-2):1-5, Mutation research
— id: 105340, year: 2009, vol: 671, page: 1, stat: Journal Article,

Splenic Infarction and Subsequent Splenic Rupture in a Patient With Paroxysmal Nocturnal Hemoglobinuria and Heparin-Induced Thrombocytopenia
Magnan, H; Kayton, ML; DiMichele, DM; Araten, DJ; Kernan, NA; Boulad, F
2009 SEP ;53(3):472-474, Pediatric blood & cancer
— id: 101298, year: 2009, vol: 53, page: 472, stat: Journal Article,

Co-Existance of JAK(V617F) and PIG-A mutations in Primary Budd-Chiari Syndrome
Sugimori, C; Shain, KH; Caceres, G; Sokol, L; Araten, D; Maciejewski, JP; Zou, JX; Epling-Burnette, PK; List, AF
2009 NOV 20 ;114(22):1237-1237, Blood
— id: 109996, year: 2009, vol: 114, page: 1237, stat: Journal Article,

Multiple myeloma involving skin and pulmonary parenchyma after autologous stem cell transplantation
Yuan, Yuan; Wieczorek, Rosemary; Green, David L; Cook, Perry; Ballard, Harold; Araten, David J
2009 ;2:48-48, Journal of hematology & oncology
— id: 105651, year: 2009, vol: 2, page: 48, stat: Journal Article,

Spontaneously Arising Red Cells with a McLeod-Like Phenotype in Normal Donors
Araten, DJ; Sanders, KJ; Pu, J; Lee, S
2008 NOV 16 ;112(11):993-993, Blood
— id: 93290, year: 2008, vol: 112, page: 993, stat: Journal Article,

A novel measurement of the rate of spontaneous mutations in human myeloid cells
Araten, DJ; Mulloy, JC; Krejci, O; DiTata, K
2007 NOV 16 ;110(11):540A-540A, Blood
— id: 76180, year: 2007, vol: 110, page: 540A, stat: Journal Article,

The mutation rate in PIG-A is normal in patients with paroxysmal nocturnal hemoglobinuria (PNH)
Araten, David J; Luzzatto, Lucio
2006 Jul 15;108(2):734-736, Blood
— id: 67529, year: 2006, vol: 108, page: 734, stat: Journal Article,

The PIG-A gene is hypermutable in lymphoid neoplasms
DiTata, K; Araten, DJ
2006 NOV 16 ;108(11):678A-678A, Blood
— id: 71381, year: 2006, vol: 108, page: 678A, stat: Journal Article,

A quantitative measurement of the human somatic mutation rate
Araten, David J; Golde, David W; Zhang, Rong H; Thaler, Howard T; Gargiulo, Lucia; Notaro, Rosario; Luzzatto, Lucio
2005 Sep 15;65(18):8111-8117, Cancer research
— id: 59005, year: 2005, vol: 65, page: 8111, stat: Journal Article,

High incidence of thrombosis in African-American and Latin-American patients with Paroxysmal Nocturnal Haemoglobinuria
Araten, David J; Thaler, Howard T; Luzzatto, Lucio
2005 Jan;93(1):88-91, Thrombosis & haemostasis
— id: 57706, year: 2005, vol: 93, page: 88, stat: Journal Article,

Severe telomere shortening in patients with paroxysmal nocturnal hemoglobinuria affects both GPI- and GPI+ hematopoiesis
Karadimitris, Anastasios; Araten, David J; Luzzatto, Lucio; Notaro, Rosario
2003 Jul 15;102(2):514-516, Blood
— id: 57707, year: 2003, vol: 102, page: 514, stat: Journal Article,

Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones
Araten, D J; Bessler, M; McKenzie, S; Castro-Malaspina, H; Childs, B H; Boulad, F; Karadimitris, A; Notaro, R; Luzzatto, L
2002 Nov;16(11):2243-2248, Leukemia
— id: 57708, year: 2002, vol: 16, page: 2243, stat: Journal Article,

Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria
Araten DJ; Swirsky D; Karadimitris A; Notaro R; Nafa K; Bessler M; Thaler HT; Castro-Malaspina H; Childs BH; Boulad F; Weiss M; Anagnostopoulos N; Kutlar A; Savage DG; Maziarz RT; Jhanwar S; Luzzatto L
2001 Nov;115(2):360-368, British journal of haematology
— id: 57710, year: 2001, vol: 115, page: 360, stat: Journal Article,

Association of clonal T-cell large granular lymphocyte disease and paroxysmal nocturnal haemoglobinuria (PNH): further evidence for a pathogenetic link between T cells, aplastic anaemia and PNH
Karadimitris A; Li K; Notaro R; Araten DJ; Nafa K; Thertulien R; Ladanyi M; Stevens AE; Rosenfeld CS; Roberts IA; Luzzatto L
2001 Dec;115(4):1010-1014, British journal of haematology
— id: 57709, year: 2001, vol: 115, page: 1010, stat: Journal Article,

Allogeneic bone marrow transplantation for paroxysmal nocturnal hemoglobinuria
Araten DJ; Luzzatto L
2000 Jan;85(1):1-2, Haematologica (Roma)
— id: 57712, year: 2000, vol: 85, page: 1, stat: Journal Article,

Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis of paroxysmal nocturnal hemoglobinuria
Karadimitris A; Manavalan JS; Thaler HT; Notaro R; Araten DJ; Nafa K; Roberts IA; Weksler ME; Luzzatto L
2000 Oct 1;96(7):2613-2620, Blood
— id: 57711, year: 2000, vol: 96, page: 2613, stat: Journal Article,

Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals
Araten DJ; Nafa K; Pakdeesuwan K; Luzzatto L
1999 Apr 27;96(9):5209-5214, Proceedings of the National Academy of Sciences of the United States of America
— id: 57713, year: 1999, vol: 96, page: 5209, stat: Journal Article,

In vitro alloreactivity against host antigens in an adult HLA-mismatched bone marrow transplant recipient despite in vivo host tolerance
Araten DJ; Lawton T; Ferrara J; Antin JH; Milford E; Carpenter CB; Maziarz RT
1993 Jan;55(1):76-82, Transplantation
— id: 57714, year: 1993, vol: 55, page: 76, stat: Journal Article,

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