Waldenström macroglobulinemia cells show only minimal changes in cytogenetic and gene expression studies. Their miRNA signature however differs from their normal counterpart. It is therefore believed that epigenetic modifications play a crucial role in the disease.Comparative genomic hybridization identified the following chromosomal abnormalities: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q. FGFR3 is overexpressed. The following signalling pathways have been implicated:

CD154/CD40
Akt
ubiquitination, p53 activation, cytochrome c release
NF-κB
WNT/beta-catenin
mTOR
ERK
MAPK
Bcl-2The protein Src tyrosine kinase is overexpressed in Waldenström macroglobulinemia cells compared with control B cells. Inhibition of Src arrests the cell cycle at phase G1 and has little effect on the survival of Waldenström macroglobulinemia or normal cells. MicroRNAs involved in Waldenström:
increased expression of miRNAs-363*, -206, -494, -155, -184, -542–3p. decreased expression of miRNA-9*.MicroRNA-155 regulates the proliferation and growth of Waldenström macroglobulinemia cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways.In Waldenström macroglobulinemia cells, histone deacetylases and histone-modifying genes are de-regulated. Bone marrow tumour cells express the following antigen targets CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%). Pathophysiology
Symptoms including blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomenon or cryoglobulinemia. Other symptoms of Waldenström macroglobulinemia are due to hyperviscosity syndrome, which is present in 6–20% of patients.
According to the model, factors predicting reduced survival are:

Age > 65 years
Hemoglobin ≤ 11.5 g/dL
Platelet count ≤ 100×109/L
B2-microglobulin > 3 mg/L
Serum monoclonal protein concentration > 70 g/LThe risk categories are:

Low: ≤ 1 adverse variable except age
Intermediate: 2 adverse characteristics or age > 65 years
High: > 2 adverse characteristicsFive-year survival rates for these categories are 87%, 68% and 36%, respectively. The corresponding median survival rates are 12, 8, and 3.5 years.The International Prognostic Scoring System for Waldenströms Macroglobulinemia has been shown to be reliable. It is also applicable to patients on a rituximab-based treatment regimen. An additional predictive factor is elevated serum lactate dehydrogenase (LDH). Epidemiology
Of cancers involving the lymphocytes, 1% of cases are Waldenström macroglobulinemia.Waldenström macroglobulinemia is a rare disorder, with fewer than 1,500 cases occurring in the United States annually. The median age of onset is between 60 and 65 years, with some cases occurring in late teens. History
Waldenström macroglobulinemia was first described by Jan G. Waldenström (1906–1996) in 1944 in two patients with bleeding from the nose and mouth, anemia, decreased levels of fibrinogen in the blood (hypofibrinogenemia), swollen lymph nodes, neoplastic plasma cells in bone marrow, and increased viscosity of the blood due to increased levels of a class of heavy proteins called macroglobulins.For a time, Waldenström macroglobulinemia was considered to be related to multiple myeloma because of the presence of monoclonal gammopathy and infiltration of the bone marrow and other organs by plasmacytoid lymphocytes.