ACUTE MYELOID LEUKEMIA (AML)

• AML is a heterogenous disease characterised by infiltration of malignant myeloid cells into blood, bone marrow.
• AML is due to inhibition of maturation of myeloid stem cells due to mutations.
• Seen in mainly in adults (50 years).
• Chromosomal mutations in AML are

1. translocation t (8: 21) & t (15: 17)
2. Inversion  16 or t (16: 16)

Etiology-

• Hereditary – Down syndrome, Klinefelter’s Syndrome, Patau Syndrome.
• Radiation
• Chemical- smoking

Pathogenesis-

• t (8: 21) disrupt the RUNXL gene & Inv (16) disrupts the CDF1β gene both have good prognosis.
• t (15: 17) (acute promyelocytic leukaemia-M3) have good prognosis.
• Gene mutation encoding components of cohesion complex.
• Most common congenital AML (in infants) are AML M5 (acute monocytic leukemia)
• Most common AML in children is AML M7 (acute megakaryoblastic anaemia)
• Most common translocation- MLL gene rearrangements on chromosome 11q.
• Monosomy is associated with a poor prognosis. 

Clinical features-

1. Due to bone marrow failure-

• Anaemia
• Bruises, petechiae, bleeding from gum
• Infection
• Fever

2. Due to organ infiltration-

• Pain & tenderness of bones
• Lymphadenopathy, enlargement of tonsils
• Splenomegaly
• Hepatomegaly
• Gum hypertrophy
• Chloroma

Investigations-

1. Blood picture-

• Anemia
• Thrombocytopenia
• WBC increased

2. Bone marrow examination

• Cellularity- marrow is hypercellular but blood tap or dry tap is seen.
• Leukemic cells- Blast cell count >20% (WHO)
• Dyserythropoiesis, megaloblastic features & ring sideroblasts are common.
• Megakaryocytes.

3. Cytochemistry-

• Myeloperoxidase- Positive in immature myeloid cells containing granules & Auer rods (most definitive sign of myeloid differentiation)
• Cluster of Auer rods called as Faggot.
• Auer rods, distinctive needle like azurophilic granules,they are particularly numerous in AML with the t (15: 17) (acute promyelocytic leukaemia-M3).
• Non specific esterase (NSE)- positive in monocytic series (M3, M4 & M5)
• Investigation of choice is flow cytometry.

Treatment-

• Blood transfusion & platelet transfusion.
• Cytotoxic drug therapy- most effective treatment of AML is cytosine, arabinoside, anthracyclines.
• Promyelocytic leukemia (M3)- tretinoin orally
• Bone marrow transplantation.