KEGG   DISEASE: H00010Help
Entry
H00010                      Disease                                

Name
Multiple myeloma
Description
Multiple myeloma is a disorder in which malignant plasma cells accumulate, generally derived from one clone in the bone marrow. Intricate interactions occur between the bone-marrow microenvironment and the myeloma cells, frequently causing bone destruction, which in turn stimulates tumor growth. Often it is preceded by a premalignant tumor called monoclonal gammopathy of undetermined significance (MGUS). Multiple oncogenic events have been identified that have contributed to the pathogenesis of myeloma. Among the earliest genetic events are translocations of the immunoglobulin heavy-chain gene locus, which leads to dysregulation of oncogenes at translocation partner regions (cyclin D1 at 11q13, FGFR3/MMSET at 4p16.3, c-MAF at 16q23, and cyclin D3 at 6p21), and deletions of 13q14, the site of a putative tumor suppressor gene. Additional molecular events include epigenetic changes and activation of oncogenes (mutations of N-RAS and K-RAS, and changes in c-MYC), which are usually associated with disease progression.
Category
Cancer
BRITE hierarchy
Pathway
Transcriptional misregulation in cancers
Gene
CCND1-IgH (translocation) [HSA:595] [KO:K04503 K06856]
CCND3-IgH (translocation) [HSA:896] [KO:K10152 K06856]
IgH-FGFR3 (translocation) [HSA:2261] [KO:K06856 K05094]
IgH-MMSET (translocation) [HSA:7468] [KO:K06856 K11424]
IgH-MAF (translocation) [HSA:4094] [KO:K06856 K09035]
N-ras (activating mutation) [HSA:4893] [KO:K07828]
K-ras (activating mutation) [HSA:3845] [KO:K07827]
c-MYC (dysregulation) [HSA:4609] [KO:K04377]
p53 (mutation) [HSA:7157] [KO:K04451]
Marker
Creatinine [CPD:C00791]
Calcium [CPD:C00076]
LDH [HSA:3939 3945 3948 197257]
B2M [HSA:567]
Monoclonal protein
CD56 [HSA:4684 4685]
Drug
Vincristine [DR:D02197]
Doxorubicin [DR:D03899 D01275]
Dexamethasone [DR:D00292 D00975 D01510 D01615 D01632 D01948 D02174 D02273 D02591 D02592]
Melphalan [DR:D00369]
Prednisone [DR:D00473]
Cyclophosphamide [DR:D00287]
Carmustine [DR:D00254]
Thalidomide [DR:D00754]
Comment
ICD-O: 9732/3, Tumor type: Plasma cell myeloma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:15031034 (description)
  Authors
Sirohi B, Powles R
  Title
Multiple myeloma.
  Journal
Lancet 363:875-87 (2004)
Reference
PMID:12965277 (description, gene)
  Authors
Seidl S, Kaufmann H, Drach J
  Title
New insights into the pathophysiology of multiple myeloma.
  Journal
Lancet Oncol 4:557-64 (2003)
Reference
PMID:12358886 (gene)
  Authors
Joy Ho P
  Title
Chromosomal and genetic abnormalities in myeloma.
  Journal
Clin Lab Haematol 24:259-69 (2002)
Reference
PMID:16155016 (gene, tumor type)
  Authors
Bergsagel PL, Kuehl WM.
  Title
Molecular pathogenesis and a consequent classification of multiple myeloma.
  Journal
J Clin Oncol 23:6333-8 (2005)
Reference
PMID:12370633 (gene)
  Authors
Podczaski E, Cain J.
  Title
Multiple myeloma.
  Journal
Clin Obstet Gynecol 45:928-38 (2002)
Reference
PMID:9414264 (gene)
  Authors
Hallek M, Bergsagel PL, Anderson KC.
  Title
Multiple myeloma: increasing evidence for a multistep transformation process.
  Journal
Blood 91:3-21 (1998)
Reference
PMID:11607813 (gene)
  Authors
Bergsagel PL, Kuehl WM
  Title
Chromosome translocations in multiple myeloma.
  Journal
Oncogene 20:5611-22 (2001)
Reference
PMID:16762540 (marker)
  Authors
San Miguel JF, Gutierrez NC, Mateo G, Orfao A.
  Title
Conventional diagnostics in multiple myeloma.
  Journal
Eur J Cancer 42:1510-9 (2006)
Reference
PMID:15061198 (marker)
  Authors
Sahara N, Takeshita A.
  Title
Prognostic significance of surface markers expressed in multiple myeloma: CD56 and other antigens.
  Journal
Leuk Lymphoma 45:61-5 (2004)
Reference
(drug)
  Authors
McPhee SJ, Papadakis MA, Tierney LM (ed).
  Title
Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition
  Journal
The McGraw-Hill Companies, Inc. (2007)

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