A New Entity?: Distinctive Immunophenotype in Non-Down Syndrome Pediatric Acute Megakaryoblastic Leukemia
Linlin Wang, Brian Levenson, Nitin J Karandikar, Jacqueline Emmons. UTSW Medical Center, Dallas, TX
Background: Acute megakaryoblastic leukemia (AMKL) is a rare acute myeloid leukemia most often seen in children with Down syndrome. AMKL in Down-syndrome children (AKML-DS) has a superior outcome when treated with high-dose cytarabine chemotherapy. However, AMKL in children without Down syndrome (AKML-nDS) is associated with a much poorer prognosis. The immunophenotypic and molecular features of AMKL-nDS are not well characterized. Here, we describe distinct and consistent immunophenotypic features we have identified in pediatric AMKL-nDS.
Design: We retrospectively searched our databases to identify all cases of pediatric AMKL-nDS from 1995 to 2012 (17 years). AMKL-DS was excluded from our study. Immunophenotypic features were assessed by 3- or 4-color flow cytometry (FC). Morphologic evaluations were performed, and immunohistochemistry (IHC) was performed when sufficient tissue was available. The medical record was reviewed for pertinent clinical findings.
Results: A total of 8 cases of AKML-nDS were identified. Of these, 7 (87.5%) showed distinct immunophenotypic features and characteristic clinical presentation, including young age (range 6m-2y) and varying degrees of extramedullary involvement with frequent hepatosplenomegaly. AMKL-nDS blasts were CD36(-), with bright CD56 and CD33 expression. CD45 was negative or only dimly expressed. Myeloid markers CD13, CD11b and CD15 were negative. Megakaryocytic markers CD41 and CD61 were positive by FC (Table 1). Blasts showed cytologic features typical for megakaryoblasts such as cytoplasmic blebs. IHC was performed on 5 cases, confirming CD61 expression in 1 case (20%) and showing CD31 in 4 cases (80%). Factor VIII was negative in all cases. t(1;22) was not identified in AMKL-nDS. Of 6 patients for whom we have follow-up, 3 died from disease 3 months to 3 years after diagnosis. Three patients diagnosed in 2012 continue to have FC evidence of residual disease.
Conclusions: We identified a subset of pediatric AMKL-nDS with a distinctive immunophenotype and aggressive clinical presentation that hint at a common underlying molecular biology. Additional studies may help elucidate the molecular mechanisms involved in its pathogenesis and better define this leukemia as a potentially distinct disease entity.
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