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Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"<p>It is not clear what causes Waldenström macroglobulinemia, though it is likely to result from a combination of genetic changes. The most common known genetic change associated with this condition is a variant (also called mutation) in the MYD88 gene, which is found in more than 90 percent of affected individuals. Another gene commonly associated with Waldenström macroglobulinemia, CXCR4, is altered in approximately 30 percent of affected individuals (most of whom also have the MYD88 gene variant).</p><p>The proteins produced from the MYD88 and CXCR4 genes are both involved in signaling within cells. The MyD88 protein relays signals that help prevent the self-destruction (apoptosis) of cells, thus aiding in cell survival. The CXCR4 protein stimulates signaling pathways inside the cell that help regulate cell growth and division (proliferation) and cell survival. Variants in these genes lead to production of proteins that are constantly turned on (overactive). Excessive signaling through these overactive proteins allows survival and proliferation of abnormal cells that should undergo apoptosis, which likely contributes to the accumulation of lymphoplasmacytic cells in Waldenström macroglobulinemia.</p><p>Other genetic changes believed to be involved in Waldenström macroglobulinemia have not yet been identified. Studies have found that certain regions of DNA are deleted or added in some people with the condition; however, researchers are unsure which genes in these regions are important for development of the condition. The variants that cause Waldenström macroglobulinemia are acquired during a person&#x27;s lifetime and are present only in the abnormal blood cells.</p><p class=\"section-source\"><a href=\"https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/#causes\">MedlinePlus Genetics: Causes</a></p>","key":"forms","title":"What causes Waldenström macroglobulinemia?"},{"bodyHtml":"<p>Waldenström macroglobulinemia usually begins in a person&#x27;s sixties and is a slow-growing (indolent) cancer. Some affected individuals have elevated levels of IgM and lymphoplasmacytic cells but no symptoms of the condition; in these cases, the disease is usually found incidentally by a blood test taken for another reason. These individuals are diagnosed with smoldering (or asymptomatic) Waldenström macroglobulinemia. It can be many years before a person with the condition develops noticable signs and symptoms.</p><p>The most common signs and symptoms to first appear in people with Waldenström macroglobulinemia are weakness and extreme tiredness (fatigue) caused by a shortage of red blood cells (anemia). Affected individuals can also experience general symptoms such as fever, night sweats, and weight loss. Some people with Waldenström macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). Doctors are unsure why this feature occurs, although they speculate that the IgM protein attaches to the protective covering of nerve cells (myelin) and breaks it down. The damaged nerves cannot carry signals normally, leading to neuropathy.</p><p>Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy). In the bone marrow, the lymphoplasmacytic cells interfere with normal blood cell development, causing a shortage of healthy blood cells (pancytopenia).</p><p>Several other signs and symptoms of Waldenström macroglobulinemia are related to the excess amounts of IgM. Increased IgM can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. Features related to hyperviscosity syndrome include bleeding in the nose or mouth, blurring or loss of vision, headache, dizziness, and confusion. In some affected individuals, IgM and other immunoglobulins react to cold temperatures to form gel-like clumps that block blood flow in areas exposed to the cold, such as the hands and feet. These clumped proteins are referred to as cryoglobulins, and their clumping causes a condition known as cryoglobulinemia. Cryoglobulinemia can lead to pain in the hands and feet or episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperatures. The IgM protein, along with another protein called amyloid, can build up in organs and interfere with their normal function. This buildup causes a condition called amyloidosis. Organs that are typically affected by amyloidosis include the heart, kidneys, liver or spleen. Affected individuals can experience weakness, fatigue, shortness of breath, irregular heartbeat, or joint pain.</p><p class=\"section-source\">Source: <a href=\"https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia\">MedlinePlus Genetics</a></p>","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"waldenstrom-macroglobulinemia","sourceDocuments":[{"name":"Waldenström macroglobulinemia","reviewed":"2015-03","sections":{"causes":{"fetchedAt":"2026-10-20T20:25:45.628754+00:00","label":"Causes","pageSha256":"ebcd6449b7c209fbb6721149bd496f1b5ace28c25fd06e99a7a9085c1eff749d","sourceUrl":"https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. Feature values below retain their original sources and patient groups.","title":"Waldenström macroglobulinemia"},"schemaVersion":1}