Waldenström's macroglobulinemia pathophysiology: Difference between revisions
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*Development of Waldenström macroglobulinemia is the result of multiple [[genetic mutations]].<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> | *Development of Waldenström macroglobulinemia is the result of multiple [[genetic mutations]].<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> | ||
*Somatic mutations as well as [[Chromosome abnormality|chromosomal abnormalities]] play a part in the pathogenesis of this disease: | *Somatic mutations as well as [[Chromosome abnormality|chromosomal abnormalities]] play a part in the pathogenesis of this disease: | ||
**A mutation of the [[MYD88|MYD88 gene]] (L265P) has been found in more than 90% of patients with Waldenström macroglobulinemia, while it has rarely presented in patients with other types of mature B-cell tumors.<ref>{{Cite journal | **A mutation of the [[MYD88|MYD88 gene]] (L265P) has been found in more than 90% of patients with Waldenström macroglobulinemia, while it has rarely presented in patients with other types of mature B-cell tumors.<ref name="TreonXu2012">{{cite journal|last1=Treon|first1=Steven P.|last2=Xu|first2=Lian|last3=Yang|first3=Guang|last4=Zhou|first4=Yangsheng|last5=Liu|first5=Xia|last6=Cao|first6=Yang|last7=Sheehy|first7=Patricia|last8=Manning|first8=Robert J.|last9=Patterson|first9=Christopher J.|last10=Tripsas|first10=Christina|last11=Arcaini|first11=Luca|last12=Pinkus|first12=Geraldine S.|last13=Rodig|first13=Scott J.|last14=Sohani|first14=Aliyah R.|last15=Harris|first15=Nancy Lee|last16=Laramie|first16=Jason M.|last17=Skifter|first17=Donald A.|last18=Lincoln|first18=Stephen E.|last19=Hunter|first19=Zachary R.|title=MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia|journal=New England Journal of Medicine|volume=367|issue=9|year=2012|pages=826–833|issn=0028-4793|doi=10.1056/NEJMoa1200710}}</ref><ref name="pmid23355535">{{cite journal| author=Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R et al.| title=Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms. | journal=Blood | year= 2013 | volume= 121 | issue= 13 | pages= 2522-8 | pmid=23355535 | doi=10.1182/blood-2012-09-457101 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23355535 }} </ref><ref name="pmid26231802">{{cite journal| author=Shi M, Spurgeon S, Press R, Olson S, Fan G| title=MYD88 mutation analysis of a rare composite chronic lymphocyte leukemia and lymphoplasmacytic lymphoma by flow cytometry cell sorting. | journal=Ann Hematol | year= 2015 | volume= 94 | issue= 11 | pages= 1941-4 | pmid=26231802 | doi=10.1007/s00277-015-2460-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26231802 }} </ref><ref name="pmid23836557">{{cite journal| author=Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ et al.| title=A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. | journal=Blood | year= 2013 | volume= 122 | issue= 7 | pages= 1222-32 | pmid=23836557 | doi=10.1182/blood-2012-12-475111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23836557 }} </ref><ref name="pmid21179087">{{cite journal| author=Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH et al.| title=Oncogenically active MYD88 mutations in human lymphoma. | journal=Nature | year= 2011 | volume= 470 | issue= 7332 | pages= 115-9 | pmid=21179087 | doi=10.1038/nature09671 | pmc=5024568 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21179087 }} </ref><ref name="pmid24224040">{{cite journal| author=Mori N, Ohwashi M, Yoshinaga K, Mitsuhashi K, Tanaka N, Teramura M et al.| title=L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma. | journal=PLoS One | year= 2013 | volume= 8 | issue= 11 | pages= e80088 | pmid=24224040 | doi=10.1371/journal.pone.0080088 | pmc=3818242 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24224040 }} </ref><ref name="pmid29080258">{{cite journal| author=Abeykoon JP, Paludo J, King RL, Ansell SM, Gertz MA, LaPlant BR et al.| title=MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia. | journal=Am J Hematol | year= 2018 | volume= 93 | issue= 2 | pages= 187-194 | pmid=29080258 | doi=10.1002/ajh.24955 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29080258 }} </ref><ref>{{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 | ||
| Line 47: | Line 47: | ||
}}</ref> | }}</ref> | ||
***Patients with Waldenström's macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have [[hyperviscosity syndrome|hyper-viscosity syndrome]] and [[bone marrow]] involvement.<ref name="UTDR" /> | ***Patients with Waldenström's macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have [[hyperviscosity syndrome|hyper-viscosity syndrome]] and [[bone marrow]] involvement.<ref name="UTDR" /> | ||
**Many [[Cytogenetics|cytogenetic]] abnormalities were reported in Waldenström macroglobulinemia patients including a [[Deletion (genetics)|deletion]] of the long arm of [[Chromosome 6 (human)|chromosome 6]] (most common) and [[Chromosome 20 (human)|chromosome 20]], [[trisomy]] 4 and 5, and [[monosomy]] 8.<ref>{{Cite journal | **Many [[Cytogenetics|cytogenetic]] abnormalities were reported in Waldenström macroglobulinemia patients including a [[Deletion (genetics)|deletion]] of the long arm of [[Chromosome 6 (human)|chromosome 6]]q21-22.1 (most common,50%)<ref name="TreonHunter2006">{{cite journal|last1=Treon|first1=S. P.|last2=Hunter|first2=Z. R.|last3=Aggarwal|first3=A.|last4=Ewen|first4=E. P.|last5=Masota|first5=S.|last6=Lee|first6=C.|last7=Santos|first7=D. Ditzel|last8=Hatjiharissi|first8=E.|last9=Xu|first9=L.|last10=Leleu|first10=X.|last11=Tournilhac|first11=O.|last12=Patterson|first12=C. J.|last13=Manning|first13=R.|last14=Branagan|first14=A. R.|last15=Morton|first15=C. C.|title=Characterization of familial Waldenström's macroglobulinemia|journal=Annals of Oncology|volume=17|issue=3|year=2006|pages=488–494|issn=1569-8041|doi=10.1093/annonc/mdj111}}</ref> and [[Chromosome 20 (human)|chromosome 20]], somatic hypermutation in IGHV.<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>, t(9;14)(p13;q32) (50%).<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>, [[trisomy]] 4(20%)<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> and 5, and [[monosomy]] 8.<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 | ||
Revision as of 16:55, 5 February 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2] Mirdula Sharma, MBBS [3]
Overview
Waldenström macroglobulinemia is an uncontrolled clonal proliferation of terminally differentiated B lymphocytes (plasma cells), which are normally involved in humoral immunity. Genes involved in the pathogenesis of Waldenström macroglobulinemia include MYD88-L265P, and CXCR4.
Pathophysiology
- Waldenström macroglobulinemia arises from terminally differentiated B lymphocytes, which are normally involved in humoral immunity.
- It is understood that Waldenström macroglobulinemia is mediated by 2 major factors:
- The secretion of IgM paraprotein
- Causes symptoms of hyperviscosity syndrome
- The infiltration of tissues with neoplastic lymphoplasmacytic cells
- Mainly the bone marrow, spleen,and lymph nodes
- Sometimes the liver, gastrointestinal tract, lungs, kidneys, skin, eyes, and central nervous system
- The secretion of IgM paraprotein
Genetics
- The exact pathogenesis of Waldenström macroglobulinemia is not completely understood; however, its familial pattern of involvement supports the role played by genetic factors in the pathogenesis of this disease.[1][2]
- Development of Waldenström macroglobulinemia is the result of multiple genetic mutations.[3]
- Somatic mutations as well as chromosomal abnormalities play a part in the pathogenesis of this disease:
- A mutation of the MYD88 gene (L265P) has been found in more than 90% of patients with Waldenström macroglobulinemia, while it has rarely presented in patients with other types of mature B-cell tumors.[4][5][6][7][8][9][10][11]
- MYD88: The activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. Point mutation of MYD88 leads to leucine to proline substitution in codon 265 (L265P) of MYD88 and produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis.
- Monoclonal gammopathy of undetermined significance patients found to have MYD88 L265P mutation have significantly higher risk of progression to Waldenström macroglobulinemia or to other lymphoproliferative disorders.
- Less commonly (30-35%), nonsense or frameshift mutations in the C-X-C chemokine receptor type 4 (CXCR4) 5338X gene have also been reported in patients with Waldenström macroglobulinemia.[12]
- Patients with Waldenström's macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyper-viscosity syndrome and bone marrow involvement.[3]
- Many cytogenetic abnormalities were reported in Waldenström macroglobulinemia patients including a deletion of the long arm of chromosome 6q21-22.1 (most common,50%)[13] and chromosome 20, somatic hypermutation in IGHV.[14], t(9;14)(p13;q32) (50%).[14], trisomy 4(20%)[14] and 5, and monosomy 8.[15]
- A mutation of the MYD88 gene (L265P) has been found in more than 90% of patients with Waldenström macroglobulinemia, while it has rarely presented in patients with other types of mature B-cell tumors.[4][5][6][7][8][9][10][11]
Epigenetics
- Three most common epigenetic causes are DNA methylation, histone acetylation, and non-coding RNAs such as miRNAs.[16]
- Up-regulation of miRNAs 155, 184, 206, 363, 494, and 542-3p occurs in Waldenström macroglobulinemia; among which miRNA-155 has a crucial role in tumor cell growth and proliferation in Waldenström macroglobulinemia.
- Gene transcription through histone acetylation occurs following increased expression of miRNA-206 and reduced expression of miRNA-9.
Associated Conditions
Several studies showed an increased incidence of following second cancers in patients with Waldenström macroglobulinemia:[17]
- Diffuse large B-cell lymphoma
- Myelodysplastic syndrome/Acute myeloid leukemia
- Brain tumor
- Renal MALT lymphoma [18]
Microscopic Pathology
Following are the images of microscopic histology of Waldenström's macroglobulinemia:
Immunohistochemistry
Malignant cells in Waldenström macroglobulinemia:[3]
- Express pan B-cell antigens (CD19, CD20, CD22, CD79A) and CD5
- Variable expression of CD11c, CD43, and CD25
- Most express IgM surface immunoglobulin, while fewer express IgG or IgA and lack IgD
References
- ↑ Royer RH, Koshiol J, Giambarresi TR, Vasquez LG, Pfeiffer RM, McMaster ML (2010). "Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation". Blood. 115 (22): 4464–71. doi:10.1182/blood-2009-10-247973. PMC 2881498. PMID 20308603.
- ↑ Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C; et al. (2006). "Characterization of familial Waldenstrom's macroglobulinemia". Ann Oncol. 17 (3): 488–94. doi:10.1093/annonc/mdj111. PMID 16357024.
- ↑ 3.0 3.1 3.2 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 (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–9. doi:10.1038/nature09671. PMID 21179087.
- ↑ Treon, Steven P.; Xu, Lian; Yang, Guang; Zhou, Yangsheng; Liu, Xia; Cao, Yang; Sheehy, Patricia; Manning, Robert J.; Patterson, Christopher J.; Tripsas, Christina; Arcaini, Luca; Pinkus, Geraldine S.; Rodig, Scott J.; Sohani, Aliyah R.; Harris, Nancy Lee; Laramie, Jason M.; Skifter, Donald A.; Lincoln, Stephen E.; Hunter, Zachary R. (2012). "MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia". New England Journal of Medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. ISSN 0028-4793.
- ↑ Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R; et al. (2013). "Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms". Blood. 121 (13): 2522–8. doi:10.1182/blood-2012-09-457101. PMID 23355535.
- ↑ Shi M, Spurgeon S, Press R, Olson S, Fan G (2015). "MYD88 mutation analysis of a rare composite chronic lymphocyte leukemia and lymphoplasmacytic lymphoma by flow cytometry cell sorting". Ann Hematol. 94 (11): 1941–4. doi:10.1007/s00277-015-2460-6. PMID 26231802.
- ↑ Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ; et al. (2013). "A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia". Blood. 122 (7): 1222–32. doi:10.1182/blood-2012-12-475111. PMID 23836557.
- ↑ Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH; et al. (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–9. doi:10.1038/nature09671. PMC 5024568. PMID 21179087.
- ↑ Mori N, Ohwashi M, Yoshinaga K, Mitsuhashi K, Tanaka N, Teramura M; et al. (2013). "L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma". PLoS One. 8 (11): e80088. doi:10.1371/journal.pone.0080088. PMC 3818242. PMID 24224040.
- ↑ Abeykoon JP, Paludo J, King RL, Ansell SM, Gertz MA, LaPlant BR; et al. (2018). "MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia". Am J Hematol. 93 (2): 187–194. doi:10.1002/ajh.24955. PMID 29080258.
- ↑ 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 (2012). "MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia". The New England journal of medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. PMID 22931316. Unknown parameter
|month=ignored (help) - ↑ Zachary R. Hunter, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Robert J. Manning, Christina Tripsas, Christopher J. Patterson, Patricia Sheehy & Steven P. Treon (2014). "The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis". Blood. 123 (11): 1637–1646. doi:10.1182/blood-2013-09-525808. PMID 24366360. Unknown parameter
|month=ignored (help) - ↑ Treon, S. P.; Hunter, Z. R.; Aggarwal, A.; Ewen, E. P.; Masota, S.; Lee, C.; Santos, D. Ditzel; Hatjiharissi, E.; Xu, L.; Leleu, X.; Tournilhac, O.; Patterson, C. J.; Manning, R.; Branagan, A. R.; Morton, C. C. (2006). "Characterization of familial Waldenström's macroglobulinemia". Annals of Oncology. 17 (3): 488–494. doi:10.1093/annonc/mdj111. ISSN 1569-8041.
- ↑ 14.0 14.1 14.2 Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L; et al. (2017). "Waldenström Macroglobulinemia: Review of Pathogenesis and Management". Clin Lymphoma Myeloma Leuk. 17 (5): 252–262. doi:10.1016/j.clml.2017.02.028. PMC 5413391. PMID 28366781.
- ↑ 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 (2002). "Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions". Blood. 100 (8): 2996–3001. doi:10.1182/blood.V100.8.2996. PMID 12351413. Unknown parameter
|month=ignored (help) - ↑ Waldenström macroglobulinemia. International Waldenström Macroglobulinemia foundation (2015)http://www.iwmf.com/sites/default/files/docs/WM_Review_Ghobrial_Jan2014.pdf Accessed on November 12, 2015
- ↑ Morra E, Varettoni M, Tedeschi A, Arcaini L, Ricci F, Pascutto C, Rattotti S, Vismara E, Paris L, Cazzola M (2013). "Associated cancers in Waldenström macroglobulinemia: clues for common genetic predisposition". Clin Lymphoma Myeloma Leuk. 13 (6): 700–3. doi:10.1016/j.clml.2013.05.008. PMID 24070824.
- ↑ Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT (2014). "Renal MALT lymphoma associated with Waldenström macroglobulinemia". J. Formos. Med. Assoc. 113 (4): 255–7. doi:10.1016/j.jfma.2011.02.007. PMID 24685302.