Acute Megakaryoblastic Leukemia After Transient... : Journal of Pediatric Hematology/Oncology (original) (raw)

Clinical And Laboratory Observations

Acute Megakaryoblastic Leukemia After Transient Myeloproliferative Disorder With Clonal Karyotype Evolution in a Phenotypically Normal Neonate

Polski, Jacek M. M.D.; Galambos, Csaba M.D.; Gale, Gordon B. M.D.; Dunphy, Cherie H. M.D.; Evans, H. Lance M.D.; Batanian, Jacqueline R. Ph.D.

From the Department of Pathology (J.M.P.), University of South Alabama College of Medicine, Mobile, Alabama, U.S.A.; and the Department of Pathology (C.G., C.H.D., H.L.E.) and Department of Pediatrics (G.B.G., J.R.B.), St. Louis University School of Medicine, St. Louis, Missouri, U.S.A.

Submitted for publication June 8, 2000; accepted July 25, 2000.

Address correspondence and reprint requests to Jacqueline R. Batanian, Ph.D., Cardinal Glennon Children's Hospital, 1465 South Grand Boulevard, St Louis, MO 63104. E-mail: [email protected].

Abstract

We report a case of transient myeloproliferative disorder (TMD) in a neonate without features of Down syndrome (DS) with clonal karyotype evolution, after apparent spontaneous resolution of TMD, but eventually progressing to acute megakaryoblastic leukemia (AMKL). The patient had petechiae, thrombocytopenia, and blastemia. Trisomy 21 with a satellited Y chromosome (Yqs) was found in proliferating blasts. A stimulated peripheral blood culture confirmed the constitutional origin of the Yqs, but did not reveal the presence of any trisomic 21 cell. By the age of 3 months, clonal chromosome evolution in the form of an interstitial deletion of the long-arm of chromosome 13 [_del(13)(q13q31)_] was detected along with trisomy 21 in unstimulated bone marrow cultures. However, remission was achieved without treatment at the age of 4 months. Trisomy 21 and del(13)(q13q31) were not identified in either cytogenetics or fluorescence in situ hybridization studies at that time. The child was asymptomatic until the age of 20 months when anemia and thrombocytopenia prompted a bone marrow biopsy, revealing changes consistent with AMKL. The remission proceeded by clonal karyotype evolution in a neonate with TMD demonstrates that clonal karyotype evolution does not indicate an immediately progressive disease. However, the development of AMKL after TMD in this case illustrates the increased risk for leukemia in TMD cases, even without DS. The gradual clonal evolution of the blasts in our patient suggests that “multiple hits” oncogenesis applies to TMD progression to acute leukemia.