Chronic myeloid leukemia

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia or chronic granulocytic leukemia, is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of mature and maturing granulocytes (a type of white blood cell) in the bone marrow and blood. The hallmark of CML is the Philadelphia chromosome, a reciprocal translocation between chromosomes 9 and 22 — t(9;22)(q34;q11) — which creates the BCR-ABL1 fusion gene. This fusion gene encodes a constitutively active tyrosine kinase that drives the malignant proliferation of myeloid cells. CML primarily affects the hematopoietic (blood-forming) system, with secondary effects on the spleen, liver, and other organs due to leukemic cell infiltration. The disease typically progresses through three phases: a chronic phase, an accelerated phase, and a blast crisis. In the chronic phase, which may last several years, patients often present with fatigue, weight loss, night sweats, abdominal fullness or pain due to splenomegaly (enlarged spleen), and elevated white blood cell counts detected on routine blood work. Some patients are asymptomatic at diagnosis. If untreated, the disease progresses to accelerated phase and eventually blast crisis, which resembles acute leukemia and carries a poor prognosis. The treatment landscape for CML has been revolutionized by tyrosine kinase inhibitors (TKIs). Imatinib (Gleevec), the first TKI approved for CML, transformed the disease from a life-threatening condition into a manageable chronic illness for most patients. Second-generation TKIs such as dasatinib, nilotinib, and bosutinib, and the third-generation TKI ponatinib, are available for patients who are resistant to or intolerant of imatinib. Allogeneic hematopoietic stem cell transplantation remains an option for patients who fail TKI therapy or present in advanced phases. With appropriate TKI treatment, the majority of chronic-phase CML patients now achieve near-normal life expectancy. Some patients who achieve deep and sustained molecular responses may be eligible for treatment-free remission under careful monitoring.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Chronic myeloid leukemia