Chronic myelogenous leukemia

NEET PG
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Chronic myelogenous leukemia

Chronic Myelogenous Leukemia (CML) is a type of leukemia that originates in the bone marrow and primarily affects the myeloid cells, specifically granulocytes. CML is characterized by the overproduction of abnormal white blood cells, particularly granulocytes (neutrophils, eosinophils, and basophils). The excessive proliferation of these cells results from a genetic abnormality known as the Philadelphia chromosome.

Here are some key points about CML:

  1. Genetic Abnormality: The Philadelphia chromosome is a genetic abnormality resulting from a reciprocal translocation between chromosomes 9 and 22. This translocation leads to the fusion of two genes: the Abelson (ABL) gene on chromosome 9 and the breakpoint cluster region (BCR) gene on chromosome 22. The resulting BCR-ABL fusion gene produces a constitutively active tyrosine kinase enzyme, which drives the uncontrolled proliferation of myeloid cells in CML.
  2. Clinical Phases:
  • Chronic Phase: CML typically begins in the chronic phase, during which the disease progresses slowly. Many patients are asymptomatic or may have mild symptoms such as fatigue, weakness, and abdominal discomfort. Blood counts often show leukocytosis (elevated white blood cell count), particularly with an increase in granulocytes.
  • Accelerated Phase: If left untreated, CML may progress to an accelerated phase characterized by an increase in the number of blast cells in the bone marrow or peripheral blood, worsening symptoms, and resistance to treatment.
  • Blast Crisis: Blast crisis is the final phase of CML and resembles acute leukemia. It is characterized by a rapid increase in blast cells (immature precursor cells) in the bone marrow and peripheral blood. Symptoms become more severe, and patients are at high risk of complications such as bleeding, infections, and organ failure.
  1. Diagnosis:
  • Diagnosis of CML is based on clinical evaluation, blood tests (complete blood count with differential), and detection of the BCR-ABL fusion gene through molecular testing, such as polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH). Bone marrow examination may also be performed to assess the extent of disease involvement.
  1. Treatment:
  • Targeted Therapy: The mainstay of treatment for CML is targeted therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib. These drugs specifically inhibit the activity of the BCR-ABL tyrosine kinase, leading to suppression of abnormal cell proliferation and induction of remission.
  • Stem Cell Transplantation: In some cases, particularly in younger patients or those with advanced disease, stem cell transplantation (also known as bone marrow transplantation) may be considered as a curative treatment option.

Overall, with the advent of TKIs, the prognosis for patients with CML has significantly improved, and many patients can achieve long-term remission and lead productive lives with ongoing treatment and monitoring. Early diagnosis and timely initiation of therapy are crucial for optimal outcomes in CML.