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Article: AML: many new tools for discovery, not enough answers (yet).

Ilaria, Robert L

2006 Volume 30, Issue 9, Page(s) 1073–1075

MeSH term(s)	Carcinogens/metabolism ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Mutation ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Phosphorylation ; Protein Processing, Post-Translational/genetics ; Proteomics
Chemical Substances	Carcinogens ; Neoplasm Proteins
Language	English
Publishing date	2006-09
Publishing country	England
Document type	Comment ; Editorial
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2006.02.024
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Article ; Online: Pathobiology of lymphoid and myeloid blast crisis and management issues.

Ilaria, Robert L

Hematology. American Society of Hematology. Education Program

2005 , Page(s) 188–194

Abstract: Despite recent improvements in the treatment of early-stage disease, the blastic phase of chronic myeloid leukemia (CML) remains a therapeutic challenge. For imatinib-naïve patients, imatinib provided encouraging hematologic and cytogenetic benefits; ... ...

Abstract	Despite recent improvements in the treatment of early-stage disease, the blastic phase of chronic myeloid leukemia (CML) remains a therapeutic challenge. For imatinib-naïve patients, imatinib provided encouraging hematologic and cytogenetic benefits; however, the vast majority of CML blast crisis cases today arise in patients already on imatinib-based therapy. Clonal evolution and duplication of the Philadelphia chromosome continue to be associated with blastic phase transformation, but recent studies have identified BCR/ABL kinase domain mutations in 30%-40% of blast crisis patients. This implies that BCR-ABL-targeted therapy might have influenced the molecular road map to blastic transformation. In this review, we will examine the effect of imatinib on primitive CML progenitors and how this might influence the pathophysiology of blast crisis. A rational framework for deciding how best to integrate stem cell transplantation, traditional chemotherapy, imatinib, and other BCR-ABL kinase inhibitors in the care of blast crisis patients will also be discussed.
MeSH term(s)	Algorithms ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Benzamides ; Blast Crisis/chemically induced ; Blast Crisis/drug therapy ; Blast Crisis/genetics ; Blast Crisis/physiopathology ; Fusion Proteins, bcr-abl/metabolism ; Genes, abl ; Genomic Instability ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Mutation ; Piperazines/adverse effects ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Protein-Tyrosine Kinases/metabolism ; Pyrimidines/adverse effects
Chemical Substances	Antineoplastic Agents ; Benzamides ; Piperazines ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
Language	English
Publishing date	2005
Publishing country	United States
Document type	Journal Article
ISSN	1520-4383
ISSN (online)	1520-4383
DOI	10.1182/asheducation-2005.1.188
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Article: Animal models of chronic myelogenous leukemia.

Ilaria, Robert L

Hematology/oncology clinics of North America

2004 Volume 18, Issue 3, Page(s) 525–43, vii

Abstract: Of the current mouse chronic myelogenous leukemia (CML) models,the murine bone marrow (BM) transduction and transplantation model most efficiently mimics many of the central features of human CML. In this model, lethally irradiated mice are reconstituted ...

Abstract	Of the current mouse chronic myelogenous leukemia (CML) models,the murine bone marrow (BM) transduction and transplantation model most efficiently mimics many of the central features of human CML. In this model, lethally irradiated mice are reconstituted with primary murine BM cells transduced with a P210BCR/ABL retrovirus. All recipient mice develop a fatal peripheral blood and BM granulocytosis and splenomegaly, a disease termed the murine CML-like myeloproliferative disorder. This model has been used to establish the causative role of Bcr/Abl in CML, identify those signaling pathways and regions of Bcr/Abl critical for leukemogenesis, and explore the limitations of targeted CML therapy. Future refinements in this CML mouse model will make it a more effective tool for studying imatinib-resistant CML, reproducing chronic- and blastic-phase human CML, and performing CML progenitor studies.
MeSH term(s)	Animals ; Bone Marrow Cells/metabolism ; Bone Marrow Transplantation ; Disease Models, Animal ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology ; Mice ; Retroviridae/genetics ; Transduction, Genetic
Language	English
Publishing date	2004-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2004.03.003
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Article: Tyrosine kinases in AML: where do they fit in?

Ilaria, Robert L

Leukemia research

2003 Volume 28, Issue 3, Page(s) 217–218

MeSH term(s)	Acute Disease ; Cell Line, Tumor/enzymology ; Cell Transformation, Neoplastic/genetics ; DNA Mutational Analysis ; Enzyme Activation ; Enzyme Induction ; Gene Expression Regulation, Leukemic ; Genes, fms ; Humans ; Leukemia, Myeloid/enzymology ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/physiology ; Proto-Oncogene Proteins c-kit/genetics ; Proto-Oncogene Proteins c-kit/physiology ; Receptor, Macrophage Colony-Stimulating Factor/physiology
Chemical Substances	Protein-Tyrosine Kinases (EC 2.7.10.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) ; Receptor, Macrophage Colony-Stimulating Factor (EC 2.7.10.1)
Language	English
Publishing date	2003-12-02
Publishing country	England
Document type	Comment ; Editorial
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2003.07.003
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Article ; Online: Exposure-response relationship of olaratumab for survival outcomes and safety when combined with doxorubicin in patients with soft tissue sarcoma.

Jones, Robin L / Mo, Gary / Baldwin, John R / Peterson, Patrick M / Ilaria, Robert L / Conti, Ilaria / Cronier, Damien M / Tap, William D

Cancer chemotherapy and pharmacology

2018 Volume 83, Issue 1, Page(s) 191–199

Abstract: Purpose: Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab ... ...

Abstract	Purpose: Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab exposure-response relationship for progression-free survival (PFS), overall survival (OS), and safety. Methods: PFS and OS data from the 133 patients enrolled in the phase 2 study were analysed using time-to-event modelling. The effect of olaratumab on PFS/OS was explored using the trough serum concentration after cycle 1 (C Results: PFS and OS were described by models with an exponential hazard function and inhibitory E Conclusions: PFS/OS benefits occurred without a rate change in TEAEs across quartiles. Maximum benefit in OS was achieved in the upper three quartiles and a potential of early disease progression in the lower quartile of olaratumab serum exposure. These results prompted a loading dose strategy in the ongoing phase 3 STS trial.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Doxorubicin/administration & dosage ; Follow-Up Studies ; Humans ; Prognosis ; Sarcoma/drug therapy ; Sarcoma/mortality ; Sarcoma/pathology ; Survival Rate
Chemical Substances	Antibodies, Monoclonal ; Doxorubicin (80168379AG) ; olaratumab (TT6HN20MVF)
Language	English
Publishing date	2018-11-08
Publishing country	Germany
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-018-3723-4
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Article ; Online: Population Pharmacokinetic Modeling of Olaratumab, an Anti-PDGFRα Human Monoclonal Antibody, in Patients with Advanced and/or Metastatic Cancer.

Mo, Gary / Baldwin, John R / Luffer-Atlas, Debra / Ilaria, Robert L / Conti, Ilaria / Heathman, Michael / Cronier, Damien M

Clinical pharmacokinetics

2017 Volume 57, Issue 3, Page(s) 355–365

Abstract: Background and objectives: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for ... ...

Abstract	Background and objectives: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population. Methods: Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and gastrointestinal stromal tumors) as a single agent or in combination with chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM Results: The PKs of olaratumab were best described by a two-compartment PK model with linear clearance (CL). Patient body weight was found to have a significant effect on both CL and central volume of distribution (V Conclusion: The PKs of olaratumab were best described by a model with linear disposition. Patient body weight and tumor size were found to be significant covariates. The PKs of olaratumab were not affected by immunogenicity or chemotherapeutic agents.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacokinetics ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics ; Body Weight ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Doxorubicin/administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/pathology ; Nonlinear Dynamics ; Receptor, Platelet-Derived Growth Factor alpha/antagonists & inhibitors ; Survival Rate ; Time Factors ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; Doxorubicin (80168379AG) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1) ; olaratumab (TT6HN20MVF)
Language	English
Publishing date	2017-08-07
Publishing country	Switzerland
Document type	Clinical Trial, Phase II ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-017-0562-0
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Article ; Online: A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia.

Vadhan-Raj, Saroj / Abonour, Rafat / Goldman, Jonathan W / Smith, David A / Slapak, Christopher A / Ilaria, Robert L / Tiu, Ramon V / Wang, Xuejing / Callies, Sophie / Cox, Joanne / Tuttle, Jay L / Lau, Yiu-Keung / Roeland, Eric J

Journal of hematology & oncology

2017 Volume 10, Issue 1, Page(s) 73

Abstract: Background: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron ... ...

Abstract	Background: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia. Methods: Thirty-three patients with hepcidin levels ≥5 ng/mL received LY2787106 either every 3 weeks (19 patients, dose range 0.3-10 mg/kg) (part A) or weekly (14 patients, dose 10 mg/kg) (part B). LY2787106 PK/PD markers of iron and hematology biology were measured. Results: LY2787106 clearance (32 mL/h) and volume of distribution (7.7 L) were independent of dose and time, leading to a dose-proportional increase in concentration with dose. Consistent dose-dependent increases in serum iron, and transferrin saturation were seen at the 3 and 10 mg/kg dose levels, typically peaking within 24 h after LY2787106 administration and returning to baseline by day 8. Conclusions: Our findings indicate that LY2787106 was well tolerated in cancer patients with anemia and that targeting the hepcidin-ferroportin pathway by neutralizing hepcidin resulted in transient iron mobilization, thus supporting the role of hepcidin in iron regulation. Trial registration: ClinicalTrial.gov, NCT01340976.
Language	English
Publishing date	2017-03-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2429631-4
ISSN	1756-8722 ; 1756-8722
ISSN (online)	1756-8722
ISSN	1756-8722
DOI	10.1186/s13045-017-0427-x
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Article: Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo.

Sinai, Parisa / Berg, Rance E / Haynie, J Marshall / Egorin, Merrill J / Ilaria, Robert L / Forman, James

Journal of immunology (Baltimore, Md. : 1950)

2007 Volume 178, Issue 4, Page(s) 2028–2037

Abstract: Imatinib mesylate (IM) is effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia. Because its influence on CD8 T cell responsiveness in vivo is unknown, we investigated the effects of IM by analyzing the ... ...

Abstract	Imatinib mesylate (IM) is effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia. Because its influence on CD8 T cell responsiveness in vivo is unknown, we investigated the effects of IM by analyzing the response of OT-1 CD8 T cells to Listeria monocytogenes (LM) that express the cognate epitope OVA(257-264) (LM-OVA). In vitro, IM had no effect on Ag-specific expansion, cell division, cell cycle progression, or IFN-gamma expression in naive or memory OT-1 T cells. However, IM induced apoptosis of naive and memory OT-1 T cells at doses of >5 microM. At 15 microM IM, OT-1 T cells did not survive in in vitro cultures. The primary response of OT-1 T cells in vivo to LM-OVA infection was unaltered. In contrast, continuous IM treatment resulted in a diminished memory OT-1 response. The expression of IL-7Ralpha, a receptor required for memory cell survival, was lower (on OT-1 cells) in animals receiving IM. These results indicate that IM treatment affects the ability of the CD8 memory pool to respond to Ag and has the potential to increase susceptibility to infection.
MeSH term(s)	Animals ; Antigens, Bacterial/immunology ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis/immunology ; Benzamides ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cell Survival/immunology ; Dose-Response Relationship, Drug ; Epitopes, T-Lymphocyte/immunology ; Epitopes, T-Lymphocyte/metabolism ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/immunology ; Imatinib Mesylate ; Immunologic Memory/drug effects ; Interferon-gamma/biosynthesis ; Interferon-gamma/immunology ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Listeriosis/genetics ; Listeriosis/immunology ; Listeriosis/metabolism ; Mice ; Mice, Transgenic ; Piperazines/pharmacology ; Pyrimidines/pharmacology ; Receptors, Interleukin-7/biosynthesis ; Receptors, Interleukin-7/immunology
Chemical Substances	Antigens, Bacterial ; Antineoplastic Agents ; Benzamides ; Epitopes, T-Lymphocyte ; Piperazines ; Pyrimidines ; Receptors, Interleukin-7 ; Interferon-gamma (82115-62-6) ; Imatinib Mesylate (8A1O1M485B)
Language	English
Publishing date	2007-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.178.4.2028
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Article: The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemia.

Wolff, Nicholas C / Richardson, James A / Egorin, Merrill / Ilaria, Robert L

Blood

2003 Volume 101, Issue 12, Page(s) 5010–5013

Abstract: The chronic myelogenous leukemia (CML)-like myeloproliferative disorder observed in the BCR/ABL murine bone marrow transduction and transplantation model shares several features with the human disease, including a high response rate to the tyrosine ... ...

Abstract	The chronic myelogenous leukemia (CML)-like myeloproliferative disorder observed in the BCR/ABL murine bone marrow transduction and transplantation model shares several features with the human disease, including a high response rate to the tyrosine kinase inhibitor imatinib mesylate (STI571). To study the impact of chronic imatinib mesylate treatment on the CML-like illness, mice were maintained on therapeutic doses of this drug and serially monitored. Unexpectedly, despite excellent systemic control of the CML-like illness, many of the mice developed progressive neurologic deficits after 2 to 4 months of imatinib mesylate therapy because of central nervous system (CNS) leukemia. Analysis of imatinib mesylate cerebral spinal fluid concentrations revealed levels 155- fold lower than in plasma. Thus, in the mouse, the limited ability of imatinib mesylate to cross the blood-brain barrier allowed the CNS to become a sanctuary for Bcr/Abl-induced leukemia. This model will be a useful tool for the future study of novel anti-CML drugs and in better defining the mechanisms for limited imatinib mesylate penetration into the CNS.
MeSH term(s)	Animals ; Benzamides ; Blood-Brain Barrier ; Bone Marrow ; Brain Neoplasms/pathology ; Central Nervous System Diseases ; Genes, abl/genetics ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Piperazines/cerebrospinal fluid ; Piperazines/pharmacokinetics ; Piperazines/therapeutic use ; Pyrimidines/cerebrospinal fluid ; Pyrimidines/pharmacokinetics ; Pyrimidines/therapeutic use ; Spinal Cord Neoplasms/pathology ; Transfection
Chemical Substances	Benzamides ; Piperazines ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B)
Language	English
Publishing date	2003-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2002-10-3059
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Article: STAT5 signaling is required for the efficient induction and maintenance of CML in mice.

Ye, Dan / Wolff, Nicholas / Li, Li / Zhang, Shumin / Ilaria, Robert L

Blood

2006 Volume 107, Issue 12, Page(s) 4917–4925

Abstract: The role of signal transducers and activators of transcription 5 (STAT5) in chronic myelogenous leukemia (CML) is controversial. To clarify the role of STAT5 signaling in P210(BCR/ABL) leukemogenesis, P210 was introduced into primary murine STAT5A- ... ...

Abstract	The role of signal transducers and activators of transcription 5 (STAT5) in chronic myelogenous leukemia (CML) is controversial. To clarify the role of STAT5 signaling in P210(BCR/ABL) leukemogenesis, P210 was introduced into primary murine STAT5A-deficient (STAT5A(-/-)) bone marrow (BM) cells, which, unlike STAT5A/5B double knockout BM cells, have no major intrinsic hematopoietic defects. Interestingly, only 21% of mice reconstituted with P210-transduced STAT5A(-/-) BM cells developed classic CML, compared with 80% to 100% of P210/STAT5A(+/+) and P210/STAT5A(+/-)-reconstituted animals. The remainder of P210/STAT5A(-/-) animals died from an acute B-cell lymphoblastic leukemia (ALL)-like disease (32%) or a CML/ALL mix (47%), reflecting impairment in the induction and maintenance of CML, which normally predominates in this mouse model. Of mice that ultimately developed CML, P210/STAT5A(-/-) animals had prolonged survival and increased myeloid immaturity. Importantly, reconstitution of wild-type mice with BM cells coexpressing P210 and dominant-negative STAT5 also profoundly reduced the incidence of CML, without impairing the induction of ALL. Altogether, these findings indicate that STAT5 and STAT5A play an important role in the pathogenesis of the CML-like disease in mice. A greater understanding of the STAT5 target genes involved in CML induction may lead to new therapeutic targets that influence CML progenitor cell biology.
MeSH term(s)	Animals ; Bone Marrow Cells/metabolism ; Bone Marrow Cells/pathology ; Bone Marrow Transplantation ; Burkitt Lymphoma/genetics ; Burkitt Lymphoma/metabolism ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Drug Design ; Enzyme Inhibitors/therapeutic use ; Genes, abl/genetics ; Hematopoiesis/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Mice ; Mice, Knockout ; STAT5 Transcription Factor/antagonists & inhibitors ; STAT5 Transcription Factor/deficiency ; STAT5 Transcription Factor/metabolism
Chemical Substances	Enzyme Inhibitors ; STAT5 Transcription Factor ; Stat5a protein, mouse
Language	English
Publishing date	2006-03-07
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2005-10-4110
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