Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives

Abstract

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms. Both are characterized by a balanced translocation between the long arms of chromosomes 15 and 17, [t(15;17)(q24;q21)], giving rise to a unique fusion gene PML-RARA and an abnormal chimeric transcription factor (PML-RARA), which disrupts normal myeloid differentiation programs. The success of current treatments for APL is in marked contrast to the vast majority of patients with non-promyelocytic AML. The overall prognosis in non-promyelocytic AML is poor, and although there has been an improvement in overall survival in patients aged <60 years, only 30%–40% of younger patients are still alive 5 years after diagnosis. APL therapy has diverged from standard AML therapy through the empirical discovery of two agents that directly target the molecular basis of the disease. The evolution of treatment over the last 4 decades to include all-trans retinoic acid and arsenic trioxide, with chemotherapy limited to patients with high-risk disease, has led to complete remission in 90%–100% of patients in trials and rates of overall survival between 86% and 97%.

The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies

“…More recently, therapies have been developed that target specific oncoproteins that mediate the differentiation arrest of AML blast cells, thereby inducing blast cell differentiation. These therapies, which include ATRA and arsenic trioxide (ASO) for APL and Enasidenib and Ivosidenib for IDH2-and IDH1mutated AML, respectively, are well-tolerated even in elderly patients with multiple comorbidities [3][4][5]. Although data on the long-term outcomes of patients treated with Enasidenib or Ivosidenib are not yet known, the initial responses observed in patients with relapsed/refractory IDH mutant AML are encouraging.…”

Myelodysplastisches Syndrom, akute Leukämie und Stammzelltransplantation

“…Hier ist zusätz-lich ein sofortiger Therapiebeginn mit All-Trans-Retinolsäure und je nach Risikoprofil Chemotherapie bzw. Arsentrioxid essenziell [16]. [18]).…”

ATPR‐induced G0/G1 phase arrest in gastric cancer cells by regulating the binding of 14‐3‐3ε and filamin A

“…ATRA has achieved remarkable effects in treatment of hematological malignancies, but for solid tumors (such as gastric cancer), its effect is far from being satisfactory. Therefore, developing safer and more effective drugs has become an urgent need . Based on our primary pharmacodynamics screening, treatment with 4‐amino‐2‐trifluoromethyl‐phenyl retinate (ATPR) for 48‐72 hours could induce G 0 /G 1 arrest and inhibit proliferation in a variety of tumor cells, including gastric cancer cells .…”