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Monosomy 7 in Patients with Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria with Evolution into Acute Myeloid Leukemia

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Chirayu Udomsakdi Auewarakul MD, PhD*, Chintana Tocharoentanaphol PhD**,
Wanchai Wanachiwanawin MD*, Surapol Issaragrisil MD*
* Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
** DNA Center, Bangkok

Abstract


We report two cases of Thai patients with aplastic anemia/paroxysmal nocturnal hemoglobinuria
(AA/PNH) who subsequently developed acute myeloid leukemia (AML) at their terminal phase. Monosomy 7
was demonstrated upon karyotypic analysis of bone marrow in both cases at the time leukemia developed.
The first patient was a 25-year-old man diagnosed with AA at age 14, recovered from AA at age 15, developed
PNH at age 21 and turned into AML at age 25. The second patient was a 27-year-old man diagnosed with
PNH at age 22, developed severe AA at age 25 and turned into AML at age 27. This latter patient received
anti-lymphocyte globulin when he developed severe AA but did not respond well whereas the first patient
fully recovered from AA with anabolic hormone treatment. Time to diagnosis of AML in the patient who
received immunosuppressive therapy was strikingly shorter than that who received conventional androgen
therapy (2 years vs 11 years after AA, respectively). The presence of monosomy 7 in leukemic cells of both
patients emphasizes its central role in the development of AML from AA/PNH. However, other factors such as
choice of AA/PNH therapy and patient’s response may modulate the time to emergence of monosomy 7-
carrying AML clone and frank leukemia. Further studies into the biologic and genetic mechanisms involved
in the development of leukemic clone arising from AA/PNH should be explored.

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