Acute Myeloid Leukemia (AML) Definition: Acute Myeloid Leukemia (AML) is a type of cancer that affects the blood and bone marrow, characterized by the rapid proliferation of abnormal myeloid precursor cells. This leads to a failure in normal blood cell production, causing an accumulation of immature white blood cells (blasts) in the bone marrow and peripheral blood. AML is a heterogeneous disease with various subtypes, each with distinct genetic and clinical features. Pathophysiology: AML originates from mutations in hematopoietic stem or progenitor cells in the bone marrow, leading to disrupted normal hematopoiesis. These genetic mutations cause the accumulation of myeloid blasts, which fail to mature into functional blood cells. The blasts proliferate uncontrollably, displacing normal hematopoietic cells, resulting in anemia, thrombocytopenia, and leukopenia. Common genetic abnormalities in AML include chromosomal translocations (e.g., t(8;21), t(15;17)), inversions, and mutations in genes such as FLT3, NPM1, and CEBPA. Types and Classification: AML is classified into several subtypes based on the French-American-British (FAB) classification system and the more recent World Health Organization (WHO) classification. Key subtypes include: 1. Acute Promyelocytic Leukemia (APL; M3): Characterized by promyeloblasts with heavy granulation and the presence of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) fusion gene. 2. Acute Myeloid Leukemia with Minimal Differentiation (M0): Features undifferentiated myeloid blasts. 3. Acute Myeloid Leukemia with Myeloid Differentiation (M1-M2): Includes various stages of myeloid cell differentiation. 4. Acute Myeloid Leukemia with Monocytic Differentiation (M4-M5): Characterized by monoblasts and promonocytes. 5. Acute Myeloid Leukemia with Excess Blasts (M6-M7): Involves erythroid or megakaryocytic differentiation abnormalities. Clinical Presentation: The symptoms of AML can be acute and rapidly progressive:  Hematologic Symptoms: Fatigue, weakness, and pallor due to anemia; bleeding tendencies and bruising due to thrombocytopenia; frequent infections due to neutropenia.  Systemic Symptoms: Fever, weight loss, night sweats.  Organ Involvement: Splenomegaly, hepatomegaly, and occasionally lymphadenopathy. In some cases, leukemia cutis (skin lesions) or central nervous system involvement may occur. Diagnosis: Diagnosis of AML is based on a combination of clinical, laboratory, and cytogenetic findings:  Blood Tests: Peripheral blood smear shows high numbers of blasts, and a complete blood count (CBC) reveals abnormalities such as anemia and thrombocytopenia.  Bone Marrow Biopsy: Essential for confirming the diagnosis, showing >20% myeloid blasts in the bone marrow.  Immunophenotyping: Flow cytometry identifies specific surface markers (e.g., CD13, CD33) to characterize the subtype.  Cytogenetic and Molecular Studies: Detect genetic abnormalities and mutations relevant for prognosis and treatment decisions. Treatment: Treatment for AML typically involves:  Induction Therapy: High-dose chemotherapy (e.g., cytarabine and an anthracycline) aimed at achieving complete remission by reducing the blast count to <5%.  Consolidation Therapy: Further chemotherapy or hematopoietic stem cell transplantation (HSCT) to eliminate residual disease and prevent relapse.  Targeted Therapy: For specific genetic mutations (e.g., FLT3 inhibitors for FLT3 mutations, all-trans retinoic acid for APL).  Supportive Care: Includes transfusions, antibiotics, and management of complications like bleeding and infections. Prognosis: The prognosis of AML depends on various factors including age, cytogenetic abnormalities, and response to treatment. Younger patients and those with favorable genetic mutations generally have a better prognosis. Advances in treatment and supportive care have improved survival rates, but AML remains a challenging disease with significant risk for relapse and treatment-related complications. Regular monitoring and personalized treatment strategies are crucial for managing the disease effectively.