Sandbox:MGS: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
Waldenström Macroglobulinemia | Waldenström Macroglobulinemia is uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity.<ref name="HP">Waldenström's macroglobulinemia. Wikipedia (2015)https://en.wikipedia.org/wiki/Waldenström%27s_macroglobulinemia#Pathophysiology Accessed on November 6, 2015</ref> | ||
In Waldenström Macroglobulinemia, peripheral B lymphocyte are stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene, without class switching. | |||
===Genetics=== | ===Genetics=== | ||
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::*MYD88: has a role in toll-like receptor and interleukin-1 receptor signaling causing activation of transcription factors of the NF-kB family. Thus, activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. MYD88 also has role in BTK signaling which also helps in B cell growth and survival. Point mutation of MYD88 produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis. <ref name="HP">Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia. UpToDate (2015)http://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-manifestations-and-diagnosis-of-waldenstrom-macroglobulinemia?source=see_link Accessed on November 9, 2015</ref><ref name="Genetics">Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015</ref> | ::*MYD88: has a role in toll-like receptor and interleukin-1 receptor signaling causing activation of transcription factors of the NF-kB family. Thus, activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. MYD88 also has role in BTK signaling which also helps in B cell growth and survival. Point mutation of MYD88 produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis. <ref name="HP">Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia. UpToDate (2015)http://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-manifestations-and-diagnosis-of-waldenstrom-macroglobulinemia?source=see_link Accessed on November 9, 2015</ref><ref name="Genetics">Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015</ref> | ||
::* Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement. | ::* Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement. | ||
===Associated Conditions=== | ===Associated Conditions=== | ||
Revision as of 19:27, 9 November 2015
Pathogenesis
Waldenström Macroglobulinemia is uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity.[1] In Waldenström Macroglobulinemia, peripheral B lymphocyte are stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene, without class switching.
Genetics
- Development of Waldenström Macroglobulinemia is the result of multiple gene mutations.[1]
- Genes involved in pathogenesis of Waldenström Macroglobulinemia are:
- MYD88
- CXCR4
- MYD88: has a role in toll-like receptor and interleukin-1 receptor signaling causing activation of transcription factors of the NF-kB family. Thus, activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. MYD88 also has role in BTK signaling which also helps in B cell growth and survival. Point mutation of MYD88 produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis. [1][2]
- Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement.
Associated Conditions
Pathology
Gross pathology
Microscopic pathology
Immunohistochemistry
Malignant cells in Waldenström Macroglobulinemia express IgM surface immunoglobulin and lack IgD. Lymphocytic component: expresses pan B cell antigens Plasma cell component: expresses CD138 Majority of malignant cells express:
- Adhesion molecules including:
- L-selectin
- ICAM-1
- CD44
- CD11c
- Lymphocyte function associated antigen 1 (LFA-1)
References:
- ↑ 1.0 1.1 1.2 Waldenström's macroglobulinemia. Wikipedia (2015)https://en.wikipedia.org/wiki/Waldenström%27s_macroglobulinemia#Pathophysiology Accessed on November 6, 2015
- ↑ Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015