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| __NOTOC__ | | __NOTOC__ |
| {{Waldenström's macroglobulinemia}} | | {{Waldenström's macroglobulinemia}} |
| {{CMG}}{{AE}}{{RAK}} | | {{CMG}}; {{AE}} {{S.M.}}, {{RAK}}; {{GRR}} {{Nat}} |
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| ==Overview== | | ==Overview== |
| The exact cause of Waldenström macroglobulinemia has not been identified; however, the diesease has been highly associated with [[somatic]] [[mutations]] in [[MYD88]] and CXR4 genes. In addition, possible less common causes of the disease include ''[[Chromosome abnormality|chromosomal abnormalities]]'' and [[Environmental factor|environmental factors]]. | | The [[Exact test|exact]] [[Causes|cause]] of [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] has not been identified; however, the [[disease]] has been highly-[[Association (statistics)|associated]] with [[somatic]] [[mutations]] in [[MYD88]]<nowiki/>and CXR4 [[genes]]. In addition, less possible common [[Causes|cause]] of the [[disease]] includes ''[[Chromosome abnormality|chromosomal abnormalities]].'' |
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| ==Causes== | | ==Causes== |
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| === Genetic Causes === | | === Genetic Causes === |
| *Waldenström Macroglobulinemia is most probably caused by a [[somatic mutation]] in the [[MYD88]] gene (seen in 90% of cases) or CXR4 gene (seen in 30% of cases).<ref name=":0">{{Cite journal | | *[[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] is most probably [[Causes|caused]] by a [[somatic mutation]] in the [[MYD88]] [[gene]] (seen in 90% of cases) or CXR4 [[gene]] (seen in 30% of [[Case-based reasoning|cases]])<ref name=":0">{{Cite journal |
| | author = [[Steven P. Treon]], [[Lian Xu]], [[Guang Yang]], [[Yangsheng Zhou]], [[Xia Liu]], [[Yang Cao]], [[Patricia Sheehy]], [[Robert J. Manning]], [[Christopher J. Patterson]], [[Christina Tripsas]], [[Luca Arcaini]], [[Geraldine S. Pinkus]], [[Scott J. Rodig]], [[Aliyah R. Sohani]], [[Nancy Lee Harris]], [[Jason M. Laramie]], [[Donald A. Skifter]], [[Stephen E. Lincoln]] & [[Zachary R. Hunter]] | | | author = [[Steven P. Treon]], [[Lian Xu]], [[Guang Yang]], [[Yangsheng Zhou]], [[Xia Liu]], [[Yang Cao]], [[Patricia Sheehy]], [[Robert J. Manning]], [[Christopher J. Patterson]], [[Christina Tripsas]], [[Luca Arcaini]], [[Geraldine S. Pinkus]], [[Scott J. Rodig]], [[Aliyah R. Sohani]], [[Nancy Lee Harris]], [[Jason M. Laramie]], [[Donald A. Skifter]], [[Stephen E. Lincoln]] & [[Zachary R. Hunter]] |
| | title = MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia | | | title = MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia |
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| === Less Common Causes === | | === Less Common Causes === |
| Less common causes of Waldenström macroglobulinemia may include:<ref name="UTDR">{{cite journal |vauthors=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM |title=Oncogenically active MYD88 mutations in human lymphoma |journal=Nature |volume=470 |issue=7332 |pages=115–9 |year=2011 |pmid=21179087 |doi=10.1038/nature09671 |url=}}</ref><ref>{{Cite journal | | Less common [[causes]] of [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]] may include:<ref name="UTDR">{{cite journal |vauthors=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM |title=Oncogenically active MYD88 mutations in human lymphoma |journal=Nature |volume=470 |issue=7332 |pages=115–9 |year=2011 |pmid=21179087 |doi=10.1038/nature09671 |url=}}</ref><ref>{{Cite journal |
| | author = [[Roelandt F. J. Schop]], [[W. Michael Kuehl]], [[Scott A. Van Wier]], [[Gregory J. Ahmann]], [[Tammy Price-Troska]], [[Richard J. Bailey]], [[Syed M. Jalal]], [[Ying Qi]], [[Robert A. Kyle]], [[Philip R. Greipp]] & [[Rafael Fonseca]] | | | author = [[Roelandt F. J. Schop]], [[W. Michael Kuehl]], [[Scott A. Van Wier]], [[Gregory J. Ahmann]], [[Tammy Price-Troska]], [[Richard J. Bailey]], [[Syed M. Jalal]], [[Ying Qi]], [[Robert A. Kyle]], [[Philip R. Greipp]] & [[Rafael Fonseca]] |
| | title = Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions | | | title = Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions |
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| | pmid = 12351413 | | | pmid = 12351413 |
| }}</ref> | | }}</ref> |
| :*[[Chromosomal abnormalities]]: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q
| | *[[Chromosomal abnormalities]]: to see the list of all [[cytogenetic]] [[abnormalities]], click '''[[Lymphoplasmacytic lymphoma pathophysiology#Cytogenetics|here]]''' |
| *History of WM/LPL or other B-cell disorders in first-degree relatives of patient with WM.<ref name="pmid16357024">{{cite journal| author=Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C et al.| title=Characterization of familial Waldenstrom's macroglobulinemia. | journal=Ann Oncol | year= 2006 | volume= 17 | issue= 3 | pages= 488-94 | pmid=16357024 | doi=10.1093/annonc/mdj111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16357024 }} </ref><ref name="pmid17785558">{{cite journal| author=McMaster ML, Csako G, Giambarresi TR, Vasquez L, Berg M, Saddlemire S et al.| title=Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 17 | pages= 5063-9 | pmid=17785558 | doi=10.1158/1078-0432.CCR-07-0299 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17785558 }} </ref><ref name="pmid18703425">{{cite journal| author=Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O| title=Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. | journal=Blood | year= 2008 | volume= 112 | issue= 8 | pages= 3052-6 | pmid=18703425 | doi=10.1182/blood-2008-06-162768 | pmc=2569164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703425 }} </ref>
| | **[[Deletion (genetics)|Deletions]] of 6q23 and 13q14 |
| *History of precursor condition of IgM Monoclonal gammopathy of undetermined significance (MGUS) in patient of WM.<ref name="pmid12720118">{{cite journal| author=Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al.| title=Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 110-5 | pmid=12720118 | doi=10.1053/sonc.2003.50082 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720118 }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316 }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316 }} </ref><ref name="pmid16034042">{{cite journal| author=Baldini L, Goldaniga M, Guffanti A, Broglia C, Cortelazzo S, Rossi A et al.| title=Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system. | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 21 | pages= 4662-8 | pmid=16034042 | doi=10.1200/JCO.2005.06.147 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16034042 }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316 }} </ref><ref name="pmid19182202">{{cite journal| author=Landgren O, Kristinsson SY, Goldin LR, Caporaso NE, Blimark C, Mellqvist UH et al.| title=Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. | journal=Blood | year= 2009 | volume= 114 | issue= 4 | pages= 791-5 | pmid=19182202 | doi=10.1182/blood-2008-12-191676 | pmc=2716021 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182202 }} </ref>
| | **[[Gain|Gains]] of 3q13-q28, 6p and 18q |
| *Age older than 60 years.<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781 }} </ref>
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| *Personal and family history of autoimmune diseases with autoantibodies leads to 2-3 fold higher risk of developing WM, especially elevated risks are associated with following:
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| **Hepatitis C virus infection (overall 20-30% increased risk for non-Hodgkin lymohoma and 3-fold increased risk for WM).<ref name="pmid18703425">{{cite journal| author=Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O| title=Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. | journal=Blood | year= 2008 | volume= 112 | issue= 8 | pages= 3052-6 | pmid=18703425 | doi=10.1182/blood-2008-06-162768 | pmc=2569164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703425 }} </ref><ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818 }} </ref><ref name="pmid18387498">{{cite journal| author=de Sanjose S, Benavente Y, Vajdic CM, Engels EA, Morton LM, Bracci PM et al.| title=Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. | journal=Clin Gastroenterol Hepatol | year= 2008 | volume= 6 | issue= 4 | pages= 451-8 | pmid=18387498 | doi=10.1016/j.cgh.2008.02.011 | pmc=3962672 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18387498 }} </ref>
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| **HIV.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818 }} </ref>
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| **Rickettsiosis.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818 }} </ref>
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| **Sjogren syndrome.<ref name="pmid20181958">{{cite journal| author=Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I et al.| title=Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. | journal=J Natl Cancer Inst | year= 2010 | volume= 102 | issue= 8 | pages= 557-67 | pmid=20181958 | doi=10.1093/jnci/djq043 | pmc=2857799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181958 }} </ref><ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783 }} </ref>
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| **Autoimmune hemolytic anemia.<ref name="pmid20181958">{{cite journal| author=Kristinsson SY, Koshiol J, Björkholm M, Goldin LR, McMaster ML, Turesson I et al.| title=Immune-related and inflammatory conditions and risk of lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. | journal=J Natl Cancer Inst | year= 2010 | volume= 102 | issue= 8 | pages= 557-67 | pmid=20181958 | doi=10.1093/jnci/djq043 | pmc=2857799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181958 }} </ref><ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783 }} </ref>
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| **Sarcoidosis.<ref name="pmid16985251">{{cite journal| author=Landgren O, Engels EA, Pfeiffer RM, Gridley G, Mellemkjaer L, Olsen JH et al.| title=Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. | journal=J Natl Cancer Inst | year= 2006 | volume= 98 | issue= 18 | pages= 1321-30 | pmid=16985251 | doi=10.1093/jnci/djj361 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16985251 }} </ref>
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| **SLE.<ref name="pmid18263783">{{cite journal| author=Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al.| title=Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. | journal=Blood | year= 2008 | volume= 111 | issue= 8 | pages= 4029-38 | pmid=18263783 | doi=10.1182/blood-2007-10-119974 | pmc=2288717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18263783 }} </ref>
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| *Hay fever.
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| :*[[Environmental factor|Environmental factors]] including exposure to farming, [[Pesticide|pesticides]], wood dust, and organic solvents
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| :*[[Chronic (medical)|Chronic]] immune stimulation and [[autoimmune disorders|auto-immune disorders]]
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| ==References== | | ==References== |