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.