Acute myeloid leukemia (AML)

Acute myeloid leukemia (AML)


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.

Exam Important

  • 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)

Pathogenesis-

  • t (8: 21) disrupt the RUNXL gene
  • Inv (16) disrupts the CDF1β gene.
  • 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.

Investigations-

  • Leukemic cells- Blast cell count >20% (WHO)
  • Dyserythropoiesis, megaloblastic features & ring sideroblasts are common
  • Myeloperoxidase- Positive in immature myeloid cells containing granules & Auer rods (most definitive sign of myeloid differentiation)
  • Cluster of Auer rods called as Faggot.
  • Non specific esterase (NSE)- positive in monocytic series (M3, M4 & M5)
  • Investigation of choice is flow cytometry

Treatment-

  • Cytotoxic drug therapy- most effective treatment of AML is cytosine, arabinoside, anthracyclines.
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