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AML-M3; acute promyelocytic leukemia

Epidemiology: 2-3% of AML Pathology: 1) hypergranular promyelocytes 2) often many Auer rods/cell 3) may have reniform or bilobed nuclei 4) associated coagulopathy - disseminated intravascular coagulation (DIC) Genetics: 1) t(15,17) associated with better prognosis 2) abnormalities in chromosomes associated with poorer prognosis - chromosome 5, chromosome 7, chromosome 8, or chromosome 11 3) SP140 may play a role 4) t(15;17)(q24;q21) involving PML with RARA - transcript arrests leukemic cells in promyelocyte stage [2] 5) t(11;17)(q32;q21) involving ZBTB16 with RARA 6) t(5;17)(q32;q11) involving NPM1 with RARA Clinical manifestations: - bleeding from thrombocytopenia & DIC - fever, diaphoresis, malaise may be noted - disseminated intravascular coagulation (DIC) unique among acute leukemias Laboratory: - PCR/ISH for acute promyelocytic leukemia (see Genetics) - t(15;17)(q24;q21) involving PML with RARA - evidence of disseminated intravascular coagulation - complete blood count (CBC): thrombocytopenia - peripheral blood smear: schistocytes (DIC) - elevated plasma D-dimer [2] (DIC) - prothrombin time & aPTT may be elevated (DIC) - fibrinogen in plasma may be low (DIC) - complete blood count (CBC): - anemia - thrombocytopenia - peripheral blood smear: - immature granulocytes, promyelocytes - Auer rods [2] - schistocytes Management: 1) all-trans retinoic acid (ATRA) - soon as possible if acute promyelocytic leukemia is suspected without waiting for conformation [2,5] - releases block in promyelocyte maturation - alone produces remissions of short duration - resolves disseminated intravascular coagulation [2] 2) anthracyclines in combination with ATRA produce remission of longer duration & possibly cures in 50-60% of patients 3) ATRA + arsenic trioxide - may be treatment of choice for initial therapy [4] - equivalent to ATRA + anthracycline - may induce a differentiation syndrome characterized by hypoxia, pulmonary infiltrates & fever - glucocorticoids (dexmethasone) with brief interruption of therapy is effective for differentiation syndrome 4) refractory cases - arsenic trioxide is used for refractory cases [3] - butyrate is also used for refractory cases 5) allogeneic stem cell transplantation - generally NOT recommended during 1st remission

Interactions

disease interactions

Related

Auer rod chromosomal translocation t15q22:17q11 (fps, AML-M3) PCR/in-situ hybridization for acute promyelocytic leukemia promyelocyte promyelocytic leukemia protein distribution pattern retinoic acid receptor alpha; RAR-alpha; nuclear receptor subfamily 1 group B member 1 (RARA, NR1B1) transcription factor PML; tripartite motif-containing protein 19; RING finger protein 71 (PML, MYL, RNF71, TRIM19)

General

acute myeloid leukemia (AML)

References

  1. Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 726
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022
  3. Powell BL, Moser B, Stock W, Gallagher RE et al Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. PMID: 20705755
  4. Lo-Coco F, Avvisati G, Vignetti M et al Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. PMID: 23841729
  5. Altman JK, Rademaker A, Cull E et al Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res. 2013 Sep;37(9):1004-9. PMID: 23768930