High-risk acute promyelocytic leukemia with unusual T/myeloid immunophenotype successfully treated with ATRA and arsenic trioxide-based regimen

Abstract

We describe two patients with acute promyelocytic leukemia (APL) with an unusual immunophenotype with co-expression of myeloperoxidase (MPO) with cytoplasmic CD3 (cCD3) representing myeloid and T-lineage differentiation. Both harbored FLT3-ITD mutations. One additionally had a deletion in the PML gene affecting the primer binding site, thus limiting measurable residual disease (MRD) analysis during follow-up. Both patients achieved durable remission with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapy, thus mitigating the need for repetitive conventional chemotherapy cycles and allogeneic stem cell transplantation. Our report highlights the complexity and challenge of diagnosis and management of APL due to the variant immunophenotype and genetics, and underscores the importance of synthesizing information from all testing modalities. The association of the unusual immunophenotype and FLT3-ITD mutation illustrates the plasticity of the hematopoietic stem cell and the pathobiology of leukemia with mixed lineage or lineage infidelity.

Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF‐kB signaling pathways synergistically

“…19 It is of paramount importance to determine how to alleviate the side effects of ATO, while maintaining its anti-tumor efficacy, before its clinical application in HCC patients. Recent studies revealed that ATO can induce differentiation, and ATO treatment clears leukemia-initiating cells in acute promyelocytic leukemia (PML) as well as in several types of solid tumors, [20][21][22][23] which might occur through induction of differentiation in CSCs. Meanwhile, the differentiationinducing capacity of ATO and its related molecular mechanism remain poorly understood in HCC.…”

Arsenic compounds induce apoptosis through caspase pathway activation in MA‑10 Leydig tumor cells

“…Organoarsenic compounds comprise liver detoxification metabolites, including dimethylarsenic acid [DMA; (CH 3 ) 2 AsO 2 H] and 4-[N-(S-glutathionylacetyl) amino] phenylarsonic acid (GSAO) (2). It has been demonstrated that As 2 O 3 treats acute promyelocytic leukemia due to its antitumorigenic properties (3,4). Furthermore, in vitro studies have revealed that As 2 O 3 induces apoptosis in various types of cell line, including the DU145 and PC-3 (prostate cancer) (5), MDAH 2774 (ovarian cancer) (5) and TM4 (sertoli tumor) cell lines (6), and CD133 + /CD13 + liver cancer stem cells (7).…”

“…Furthermore, DMA exerts an antiproliferative and cytotoxic effect on human leukemia and multiple myeloma cells (10). Inorganic and organic arsenic compounds therefore represent novel potential therapeutic agents against solid tumors and various types of malignancy (3)(4)(5)(6)(7)(8)(9)(10).…”

Integrated bioinformatics analysis and network pharmacology to explore the potential mechanism of Patrinia heterophylla Bunge against acute promyelocytic leukemia

“…[ 46 ] MPO is highly expressed in leukemic promyelocytes and is a diagnostic biomarker for the rapid screening of APL. [ 47 , 48 ] We assumed that these 6 core targets may be therapeutic targets for APL. Based on KM curves, we found that MAPK3, MMP9, and MPO could affect the median survival time of patients with AML.…”