Small doses of ARA‐C in the treatment of acute myeloid leukaemia: differentiation of myeloid leukaemia cells?

Abstract

Three patients with acute myeloid leukaemia were treated with small doses of ARA-C (10 mg/m2/12 h, subcutaneous injections) and complete remission was obtained. The small doses of ARA-C, the progressive evolution, the absence of aplasia before remission, the simultaneous presence of normal islets of promyelocytes and leukaemic myeloblasts, favour a differentiating role for the drug rather than an antimitotic effect.

A comparison of low‐dose cytarabine and hydroxyurea with or without all‐trans retinoic acid for acute myeloid leukemia and high‐risk myelodysplastic syndrome in patients not considered fit for intensive treatment

“…Its mechanism of action at low doses is not completely clear: Some believe that it retains cytotoxic action, and some have view that it induces apoptosis by differentiation induction. 12,13 There is also a perception that LD ara-C induces excess cytopenia, thereby defeating the objectively of being optimally tolerable to the older patient. An alternative and widely used approach is to provide best supportive care, which includes blood product support and antibiotic treatment, as required with periodic treatment with hydroxyurea (HU) to control the peripheral white blood count.…”

A critical role for the co-repressor N-CoR in erythroid differentiation and heme synthesis

“…K562 cells are resistant to low doses of Ara-C in terms of apoptosis. Instead, low doses of Ara-C induce K562 cell erythroid differentiation [13]. Although how Ara-C induces K562 differentiation toward the erythroid lineage remains unclear, microarray data from Ara-C-induced K562 cells show that systemic upregulation of genes is involved in erythroid differentiation [17].…”

“…The K562 cell line was established more than 30 years ago [11] from a patient with an acute transformation of chronic myelogenous leukemia. K562 cells are multipotent stem cells and can differentiate into erythroid lineages upon induction with different chemicals, including hemin, cytosine arabinoside (Ara-C) and 5-azacytidine [12][13][14][15]. As a canonical agent for erythroid differentiation, hemin exerts a profound effect on K562 cell maturation and promotes the synthesis of the fetal and embryonic hemoglobins [16].…”

Isolation of Apoptosis- and Differentiation-Inducing Substances toward Human Promyelocytic Leukemia HL-60 Cells from Leaves ofJuniperus taxifolia

“…Differentiation-inducing therapy is therefore anticipated as a novel medical treatment that could reduce such adverse effects, when compared to previous anticancer drugs. [2][3][4][5] The human promyelocytic leukemia HL-60 cell line has been used as a model system for studying cellular differentiation. HL-60 cells can be differentiated into monocyte/macrophage-like or granulocyte-like cells by various agents such as all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D 3 , anticancer drugs and natural compounds.…”