Multiple myeloma

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.

Cancer

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]

Creatinine [CPD:C00791]
Calcium [CPD:C00076]
LDH [HSA:3939 3945 3948 197257]
B2M [HSA:567]
Monoclonal protein
CD56 [HSA:4684 4685]

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]

ICD-O: 9732/3, Tumor type: Plasma cell myeloma

PMID:15031034 (description)

Sirohi B, Powles R

Multiple myeloma.

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PMID:12965277 (description, gene)

Seidl S, Kaufmann H, Drach J

New insights into the pathophysiology of multiple myeloma.

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PMID:12358886 (gene)

Joy Ho P

Chromosomal and genetic abnormalities in myeloma.

Clin Lab Haematol 24:259-69 (2002)

PMID:16155016 (gene, tumor type)

Bergsagel PL, Kuehl WM.

Molecular pathogenesis and a consequent classification of multiple myeloma.

J Clin Oncol 23:6333-8 (2005)

PMID:12370633 (gene)

Podczaski E, Cain J.

Multiple myeloma.

Clin Obstet Gynecol 45:928-38 (2002)

PMID:9414264 (gene)

Hallek M, Bergsagel PL, Anderson KC.

Multiple myeloma: increasing evidence for a multistep transformation process.

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PMID:11607813 (gene)

Bergsagel PL, Kuehl WM

Chromosome translocations in multiple myeloma.

Oncogene 20:5611-22 (2001)

PMID:16762540 (marker)

San Miguel JF, Gutierrez NC, Mateo G, Orfao A.

Conventional diagnostics in multiple myeloma.

Eur J Cancer 42:1510-9 (2006)

PMID:15061198 (marker)

Sahara N, Takeshita A.

Prognostic significance of surface markers expressed in multiple myeloma: CD56 and other antigens.

Leuk Lymphoma 45:61-5 (2004)

(drug)

McPhee SJ, Papadakis MA, Tierney LM (ed).

Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition

The McGraw-Hill Companies, Inc. (2007)