Active compounds-based discoveries about the differentiation and apoptosis of leukemic cells

Abstract

Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies which are characterized by the blockage of hematopoietic cell differentiation with uncontrolled proliferation and/or impaired apoptosis. Over the past 20 years, there has been tremendous progress in the biological, molecular, and cytogenetic aspects of the disease, accompanied by significant advancements in the treatment of AML patients. For example, all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ) have been used clinically for effective treatments of patients with acute promyelocytic leukemia (APL, a unique subtype of AML) through differentiation and/or apoptosis induction. More intriguingly, these active compounds-based chemical biological studies greatly accelerated our understanding on leukemogenesis and targeted therapy of AML patients. Based on some recent findings mainly from our group, this review attempts to summarize the related advances from Chinese researchers. chemical biology, leukemia, cell differentiation, apoptosis Acute myeloid leukemia (AML), a heterogeneous group of hematopoietic malignancies, occurs frequently in adults. Remarkable advances in the biological, molecular and cytogenetic aspects of this disease have been made over the past 20 years. It is well-established that specific cytogenetic alterations, particularly chromosomal translocations that generate abnormal oncogenic fusion proteins, such as t(15;17) yielding PML-RARα (promyelocytic leukemia-retinoic acid receptor-alpha) and t(8;21) yielding AML1-ETO (acute myeloid leukemia 1-eight twenty-one), cause the blockage of hematopoietic cell differentiation at a certain stage, accompanied by uncontrolled proliferation and/or impaired apoptosis. On the other hand, the past decades are also marked by great advances in the treatment of AML patients. One typical example is the discovery that all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ) could effectively treat patients with acute promyelocytic leukemia (APL, also known as M3-type AML) through the induction of differentiation and/or apoptosis. Due to the relative convenience of acquiring leukemia samples and the ease of the evaluation of therapeutic effects, chemical biological methodologies that use specific, active small molecules (such as ATRA and As 2 O 3 ) as probes to investigate mechanisms of basic cellular activities greatly accelerated our understanding of leukemogenesis and targeted therapy of AML patients [1] . Based on some recent findings primarily from our group, this review attempts to summarize the related advances from Chinese researchers.

Current advances in the application of proteomics in apoptosis research

“…However, the network of apoptosis regulation is highly complex and one single drug usually does not work well. The development of novel anticancer chemotherapeutic drugs whose mechanisms of action are different from established drugs is needed for the treatment of cancer, particularly in those patients showing resistance to standard treatment [27,28]. However, the development of therapeutics from inception to marketing is a costly and time-consuming path with high attrition rates.…”