Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

Abstract

Primary myelofibrosis (PMF), per WHO criteria, is a clonal myeloproliferative neoplasm that usually presents with a proliferation of granulocytic and megakaryocytic lineages with an associated fibrous deposition and extramedullary hematopoiesis. The bone marrow histologic findings of this disorder are typically characterized by the presence of myeloid metaplasia with an associated reactive fibrosis, angiogenesis, and osteosclerosis. However, marked myelofibrosis is not solely confined to PMF and may also be associated with other conditions including but not limited to acute megakaryoblastic leukemias (FAB AML-M7). Here, we describe a rare case of a non-megakaryoblastic acute myeloid leukemia with marked myelofibrosis with osteosclerosis and an isolated trisomy 19. A 19-year-old male presented with severe bone pain of one week duration with a complete blood cell count and peripheral smear showing a mild anemia and occasional circulating blasts. A follow up computed tomography (CT) scan showed diffuse osteosclerosis with no evidence of hepatosplenomegaly or lymphadenopathy. Subsequently, the bone marrow biopsy showed markedly sclerotic bony trabeculae and a hypercellular marrow with marked fibrosis and intervening sheets of immature myeloid cells consistent with myeloblasts with monocytic differentiation. Importantly, these myeloblasts were negative for megakaryocytic markers (CD61 and vWF), erythroid markers (hemoglobin and E-cadherin), and lymphoid markers (CD3, CD19, and TdT). Metaphase cytogenetics showed an isolated triosomy 19 with no JAK2 V617F mutation. The patient was treated with induction chemotherapy followed by allogenic hematopoietic stem cell transplantation which subsequently resulted in a rapid resolution of bone marrow fibrosis, suggesting graft-anti-fibrosis effect. This is a rare case of a non-megakaryoblastic acute myeloid leukemia with myelofibrosis and osteosclerosis with trisomy 19 that may provide insights into the prognosis and therapeutic options of future cases.

PAK1 Inhibition Slows Growth and Partially Promotes Differentiation of AMKL Cells

“…Although the pathogenesis of AMKL is unclear, ~3/5 of children with AMKL have Down syndrome (DS) and present with acquired GATA1 mutations (Wechsler et al 2002);~1/3 of infants with non-DS-AMKL, have t (1; 22) (P13; q13) chromosome translocation, which leads to the expression of the OTT-MAL fusion protein (Ma et al 2001;Mercher et al 2002). The bone marrow cytology of AMKL is characterized by the expansion of megakaryoblast (Malinge et al 2009), which suppress the production of erythrocytes and granulocytes, leading to anaemia, bleeding and infection, as well as marrow brosis (Niino et al 2013;Stelling et al 2015). Although intensive chemotherapy regimens, such as high-dose cytarabine can improve the overall survival (OS) of patients with AMKL (Schweitzer et al 2015;Taga et al 2011), only by which, the complete remission (CR) of AMKL is the likelihood of relaspse low, more likely to relapse and the prognosis is still poor (Garderet et al 2005; Greene et al 2003;Maarouf et al 2019).…”