Perspective on Therapeutic Strategies of Leukemia Treatment — Focus on Arsenic Compounds

Leukemia is a type of cancer of the body’s blood-forming tissues, including the bone marrow and the lymphatic system. Treatments for leukemia are complex, depending upon the type of leukemia and other factors. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) and accounts for approximately 10-15% of all cases of AML in adults. Arsenic and its compounds are widely distributed in the environment and have been used medicinally for over 2,000 years. In fact, investigators from China and the USA have demonstrated that treatment with ATO (As2O3, AsIII) results in complete remission in 90% of relapsed APL patients since mid-1990s. Moreover, As2S2 or As4S4, also known as realgar, has been gaining increasing attention and is traditionally used to treat certain types of hematological disorders including chronic myeloid leukemia (CML), AML, myelodysplastic syndrome (MDS) and MDS/AML in China. In this chapter, we first highlight the pharmacokinetics of ATO and realgar in leukemia patients and/or healthy volunteer. We will further summarize the detailed mechanisms underlying the cytocidal effects of these arsenic compounds. We also provide detailed insight into potential future clinical application of those promising candidates endowed with potent antitumor activities in view of combination with arsenic compounds

Induced differentiation of human myeloid leukemia cells into M2 macrophages by combined treatment with retinoic acid and 1α,25-dihydroxyvitamin D3.

Retinoids and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) induce differentiation of myeloid leukemia cells into granulocyte and macrophage lineages, respectively. All-trans retinoic acid (ATRA), which is effective in the treatment of acute promyelocytic leukemia, can induce differentiation of other types of myeloid leukemia cells, and combined treatment with retinoid and 1,25(OH)2D3 effectively enhances the differentiation of leukemia cells into macrophage-like cells. Recent work has classified macrophages into M1 and M2 types. In this study, we investigated the effect of combined treatment with retinoid and 1,25(OH)2D3 on differentiation of myeloid leukemia THP-1 and HL60 cells. 9-cis Retinoic acid (9cRA) plus 1,25(OH)2D3 inhibited proliferation of THP-1 and HL60 cells and increased myeloid differentiation markers including nitroblue tetrazolium reducing activity and expression of CD14 and CD11b. ATRA and the synthetic retinoic acid receptor agonist Am80 exhibited similar effects in combination with 1,25(OH)2D3 but less effectively than 9cRA, while the retinoid X receptor agonist HX630 was not effective. 9cRA plus 1,25(OH)2D3 effectively increased expression of M2 macrophage marker genes, such as CD163, ARG1 and IL10, increased surface CD163 expression, and induced interleukin-10 secretion in myeloid leukemia cells, while 9cRA alone had weaker effects on these phenotypes and 1,25(OH)2D3 was not effective. Taken together, our results demonstrate selective induction of M2 macrophage markers in human myeloid leukemia cells by combined treatment with 9cRA and 1,25(OH)2D3

Clinical impact of central nervous system‐directed therapies on intravascular large B‐cell lymphoma: A single institution's experience

Abstract Intravascular large B‐cell lymphoma (IVLBCL) is a rare subtype of B‐cell lymphoma characterized by aggressive disease progression with a high incidence of central nervous system (CNS) involvement. We retrospectively analyzed 16 patients with de novo IVLBCL treated at our hospital between 2004 and 2018 with either standard therapy plus CNS‐directed therapy or standard therapy alone. CNS‐directed therapy was associated with a significantly better 2‐year CNS‐free survival (100% vs. 63%, p = 0.0191), despite no significant effects on progression‐free or overall survival. Further studies should assess CNS‐focused treatment in patients with IVLBCL with or without primary CNS involvement