Chronic Lymphocytic Leukemia

Oncology section

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow, leading to the overproduction of abnormal lymphocytes, a type of white blood cell. CLL is characterized by the gradual accumulation of these abnormal lymphocytes, which are unable to function properly and crowd out normal blood

cells in the bone marrow and lymphoid tissues. CLL is the most common type of leukemia in adults, comprising approximately 30% of all leukemia cases. It is more prevalent in older adults, with the median age at diagnosis being around 70 years. CLL is rare in individuals under the age of 40.

About CLL

Understanding Sympthomps

Progression and Symptoms of CLL

CLL primarily affects B lymphocytes, which are a type of white blood cell responsible for producing antibodies and coordinating the immune response against infections. In CLL, these B lymphocytes become cancerous and proliferate uncontrollably.

CLL typically progresses slowly over time, with the abnormal lymphocytes accumulating gradually in the body. In many cases, CLL is discovered incidentally during routine blood tests and may not cause symptoms in the early stages. Some individuals may live with CLL for many years without requiring treatment, while others may experience disease progression and require therapy. As CLL progresses, it can cause symptoms such as enlarged lymph nodes, particularly in the neck, armpits, and groin, as well as fatigue, weight loss, night sweats, and frequent infections. These symptoms can vary widely among individuals and may be absent in some cases.

Diagnosis and Staging of CLL

CLL is typically diagnosed through blood tests that reveal an elevated number of abnormal lymphocytes, a condition known as lymphocytosis. Additional tests, such as flow cytometry, bone marrow biopsy, and cytogenetic analysis, may be performed to confirm the diagnosis and determine the extent of the disease. CLL is staged based on the extent of disease involvement and the presence of certain prognostic factors.

The Rai staging system and the Binet staging system are commonly used to classify CLL into different stages ranging from early-stage disease with no symptoms to advanced-stage disease with significant symptoms and complications. Chronic lymphocytic leukemia (CLL) involves both germline and somatic genetic alterations that contribute to disease development and progression. Germline mutations are inherited genetic changes present in all cells of an individual's body, whereas somatic mutations are acquired alterations that occur specifically in the cancerous cells.

Germline Genes:

ATM (Ataxia Telangiectasia Mutated)

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NOTCH1

Germline polymorphisms in the NOTCH1 gene have been implicated in CLL susceptibility. NOTCH1 is involved in cell signaling pathways that regulate cell proliferation and differentiation.

TERT (Telomerase Reverse Transcriptase)

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Somatic Genes:

TP53 (Tumor Protein p53)

Somatic mutations or deletions in the TP53 gene are commonly found in aggressive forms of CLL and are associated with poor prognosis. TP53 is a tumor suppressor gene involved in cell cycle regulation and DNA repair. Loss of TP53 function can lead to unchecked cell proliferation and resistance to apoptosis.

IGHV (Immunoglobulin Heavy Variable)

Somatic mutations in the IGHV gene are commonly found in CLL and are associated with disease prognosis. IGHV mutational status is used as a prognostic marker in CLL, with patients having unmutated IGHV associated with more aggressive disease and poorer outcomes compared to those with mutated IGHV.

NOTCH1

Somatic mutations in the NOTCH1 gene are found in a subset of CLL cases and are associated with disease progression and resistance to therapy. NOTCH1 mutations can activate aberrant signaling pathways involved in cell survival and proliferation.

SF3B1 (Splicing Factor 3B Subunit 1)

Somatic mutations in the SF3B1 gene are found in a subset of CLL cases and are associated with adverse clinical outcomes. SF3B1 is involved in RNA splicing, and mutations in this gene can disrupt normal splicing patterns and contribute to CLL pathogenesis.

BIRC3 (Baculoviral IAP Repeat Containing 3)

Somatic mutations in the BIRC3 gene are associated with CLL progression and resistance to therapy. BIRC3 encodes an inhibitor of apoptosis protein (IAP) involved in regulating cell survival pathways.