W Michael Kuehl
Affiliation: National Institutes of Health
- Multiple myeloma: evolving genetic events and host interactionsW Michael Kuehl
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Naval Hospital, Maryland 20889 5105, USA
Nat Rev Cancer 2:175-87. 2002..What causes full-blown myeloma? And can our molecular understanding of this common haematological malignancy be used to develop effective preventive and treatment strategies?..
- Modeling multiple myeloma by AID-dependent conditional activation of MYCW Michael Kuehl
Genetics Branch, National Cancer Institute, Bethesda, MD 20889, USA
Cancer Cell 13:85-7. 2008..Although much remains to be done to fully characterize this model, this approach is likely to impact the creation of sporadic models for other kinds of germinal center B cell tumors...
- Classical and/or alternative NF-kappaB pathway activation in multiple myelomaYulia N Demchenko
Genetics Branch, National Cancer Institute, Bethesda, MD, USA
Blood 115:3541-52. 2010..Our results suggest that MM tumors can achieve increased autonomy from the bone marrow microenvironment by mutations that activate either NF-kappaB pathway...
- A mechanistic rationale for MEK inhibitor therapy in myeloma based on blockade of MAF oncogene expressionChristina M Annunziata
Metabolism Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr, Bethesda, MD 20892 1374, USA
Blood 117:2396-404. 2011..The data presented herein demonstrate that the MEK-ERK pathway regulates MAF transcription, providing molecular rationale for clinical evaluation of MEK inhibitors in MAF-expressing myeloma...
- Molecular pathogenesis of multiple myeloma and its premalignant precursorW Michael Kuehl
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
J Clin Invest 122:3456-63. 2012..Here we review the current understanding of myeloma pathogenesis and insight into new therapeutic strategies provided by animal models and genetic screens...
- A der(8)t(8;11) chromosome in the Karpas-620 myeloma cell line expresses only cyclin D1: yet both cyclin D1 and MYC are repositioned in close proximity to the 3'IGH enhancerAmel Dib
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889 5101, USA
DNA Repair (Amst) 8:330-5. 2009..The secondary translocation that dysregulated MYC resulted in extensive regions from both donor chromosomes being transmitted to both derivative chromosomes, suggesting a defect in DNA recombination or repair in the myeloma tumor cell...
- Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumorsAna Gabrea
Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
Genes Chromosomes Cancer 47:573-90. 2008..We conclude that IG light chain and MYC rearrangements, as well as secondary IGH rearrangements, make similar contributions to the progression of both HRD and NHRD MM tumors...
- Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myelomaChristina M Annunziata
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
Cancer Cell 12:115-30. 2007..These data demonstrate that addiction to the NF-kappaB pathway is frequent in myeloma and suggest that IKKbeta inhibitors hold promise for the treatment of this disease...
- Complex IGH rearrangements in multiple myeloma: Frequent detection discrepancies among three different probe setsGina Y Kim
Genetics Branch, National Cancer Institute, Bethesda, MD
Genes Chromosomes Cancer 53:467-74. 2014..However, the majority of complex IGH rearrangements had detection discrepancies among the three centromeric IGH probes...
- Pathogenesis of monoclonal gammopathy of undetermined significance and progression to multiple myelomaAdriana Zingone
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889 5105, USA
Semin Hematol 48:4-12. 2011..However, two models based on clinical laboratory tests indicate that it is possible to stratify MGUS tumors into groups that have average rates of progression as low as 0.26% per year and as high as 12% per year...
- Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphomaGeorg Lenz
Metabolism Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute NCI, National Institutes of Health NIH, Bethesda, MD 20892, USA
J Exp Med 204:633-43. 2007..Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB...
- Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stromaElaine M Hurt
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cancer Cell 5:191-9. 2004..The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention...
- Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myelomaSham Mailankody
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Leuk Lymphoma 51:2159-70. 2010..A better understanding of the pathogenesis will allow us to define the biological high-risk precursor disease and, ultimately, to develop early intervention strategies designed to delay and prevent full-blown MM...
- A critical role for the NFkB pathway in multiple myelomaYulia N Demchenko
Genetics Branch, National Cancer Institute, Bethesda, MD, USA
Oncotarget 1:59-68. 2010..Given the strong dependence of MGUS and MM tumors on NFkB pathway activation, inhibition by a combination of targeting extrinsic signaling plus both NFkB pathways appears to be an attractive therapeutic approach in MM tumors...
- Repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genomeMasahiro Onozawa
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 and
Proc Natl Acad Sci U S A 111:7729-34. 2014....
- Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletionsRoelandt F J Schop
Department of Hematology and Internal Medicine and the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
Blood 100:2996-3001. 2002..However, WM tumor cells, which appear to be diploid or near diploid, often have deletions of 6q21...
- Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myelomaP Leif Bergsagel
Weill Medical College of Cornell University, New York, NY 10021, USA
Immunol Rev 194:96-104. 2003..We speculate that ectopic cyclin D1 expression without t(11;14) is dependent on tumor-specific interaction with bone marrow stromal cells...
- Genetics and cytogenetics of multiple myeloma: a workshop reportRafael Fonseca
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
Cancer Res 64:1546-58. 2004..Areas in need of further study were identified. The study of the genetic aberrations will likely form the platform for targeted therapy for the disease...
- Advances in biology of multiple myeloma: clinical applicationsTeru Hideshima
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
Blood 104:607-18. 2004....
- Molecular pathogenesis and a consequent classification of multiple myelomaP Leif Bergsagel
Comprehensive Cancer Center, Division of Hematology Oncology, Mayo Clinic, Scottsdale, AZ 85259, USA
J Clin Oncol 23:6333-8. 2005....
- Cyclin D dysregulation: an early and unifying pathogenic event in multiple myelomaP Leif Bergsagel
Mayo Clinic Scottsdale, Comprehensive Cancer Center and Division of Hematology Oncology, Scottsdale, AZ, USA
Blood 106:296-303. 2005..However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor...
- The enigma of ectopic expression of FGFR3 in multiple myeloma: a critical initiating event or just a target for mutational activation during tumor progressionMarta Chesi
Weill Medical College of Cornell University, New York, USA
Curr Opin Hematol 9:288-93. 2002..However, it remains to be proven if and how dysregulation of FGFR3 or MMSET mediates an early oncogenic process in multiple myeloma...
- CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanismsFenghuang Zhan
Donna D and Donald M Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA
Blood 109:4995-5001. 2007....