Introduction
Acute myeloid leukemia (AML) is a clonal hematopoietic stem cell malignancy, which is characterized by an accumulation of immature progenitor cells with arrested differentiation causing suppression of hematopoiesis [1]. Current treatment strategies for patients with AML include combination chemotherapy, hypomethylation agents (HMAs), and/or hematopoietic stem cell transplantation (HSCT), which are generally selected based on clinical, hematological and genetic prognostic indicators [2].
Nucleoporin 98 gene (NUP98) is fused to a variety of partner genes in a spectrum of hematologic malignancies, especially pediatric leukemias with poor prognosis [3]. Nuclear receptor-binding SET domain protein 1 (NSD1) is a member of histone methyltransferases family, which are essential in development and are mutated in AML, multiple myeloma, and lung cancers [4]. About 5% of human AMLs harbor the t (5;11) (q35; p15.5) translocation, which generates NUP98-NSD1 fusion gene [5]. Gang et al. identified that NUP98-NSD1 induced AML and sustained self-renewal of myeloid stem cells in vitro [4]. Later several largescale cohort studies of patients with AML have confirmed that the presence of NUP98-NSD fusion defines a high-risk leukemia subset with a low remission and high relapse rates [6, 7].
Despite our current knowledge of the molecular mechanisms and co-occurring genetic events of AML with NUP98-NSD1 fusion, the ability to effectively treat patients with these translocations is very limited. Current therapy strategies for AML patients with NUP98-NSD1 fusion often employ chemotherapy followed by hematopoietic stem cell transplantation (HSCT) during the first complete molecular remission. However, many patients could not achieve complete remission (CR) after conventional chemotherapy. For cases with poor remission status, salvage transplantation tends to have low success rates and high recurrence rates [8].
Here we present a case of successful treatment with decitabine, aclacinomycin, cytosine arabinoside (Ara-C), granulocyte-colony stimulating factor (DCAG) plus Bcl-2 inhibitor, venetoclax in a patient with AML (M2) expressing NUP98-NSD1 fusion, followed by allogeneic HSCT, who had never achieved CR after two courses of conventional chemotherapy regimens.