Ham-Wasserman lecture: treatment of acute leukemia by inducing differentiation and apoptosis.

  title={Ham-Wasserman lecture: treatment of acute leukemia by inducing differentiation and apoptosis.},
  author={Zhen-yi Wang},
  journal={Hematology. American Society of Hematology. Education Program},
  • Zhen-yi Wang
  • Published 2003
  • Medicine, Biology
  • Hematology. American Society of Hematology. Education Program
Conventional treatment of acute leukemia involves the use of cytotoxic agents (chemotherapy), but other strategies have been explored. All-trans retinoic acid (ATRA) and arsenic have clearly been effective in the treatment of acute promyelocytic leukemia (APL), which creates the possibility that other types of acute leukemia can be conquered by selectively inducing differentiation and/or apoptosis. A great number of investigations have been performed to elucidate the mechanisms and search for… 

Tables from this paper

Acute promyelocytic leukemia: A model of molecular target based therapy

The development of curative approaches for acute promyelocytic leukemia (APL) may serve as a paradigm for other hematological malignancies and shed new lights on leukemogenesis, gain insights into therapeutic mechanisms, and provide opportunities for designing more rational therapies.

Acute promyelocytic leukemia: recent advances in therapy and molecular basis of response to arsenic therapies

Recent findings that reveal why a traditional poison has become a magical potion for a major type of APL are reviewed, which is characterized by a balanced chromosomal translocation t(15;17).

Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy

The story of APL can serve as a model for the development of curative approaches for disease and suggests that molecularly synergistic targeted therapies are powerful tools in cancer, and dissection of disease pathogenesis or anatomy of the cancer genome is critical in developing molecular target-based therapies.

Acute promyelocytic leukemia: from highly fatal to highly curable.

The history of introduction of ATRA and ATO into clinical use and the mechanistic studies in understanding this model of cancer targeted therapy are reviewed.

Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia

It is concluded that APL patients may benefit from the use of the combination of ATRA and As2O3 in either remission induction or consolidation/maintenance.

Treatment of Acute Promyelocytic Leukemia with Single Agent Arsenic Trioxide: Experience from a Tertiary Care Center in India

Arsenic trioxide as single agent can be offered as a standard alternative regimen to ATRA based chemotherapy in patients with economic constraints in patients of newly diagnosed APML.

From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemia.

The successful revival of arsenic in acute promyelocytic leukemia, together with modern mechanistic studies, has thus allowed a new paradigm to emerge in translational medicine.

Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity.

Single-agent As2O3, as used in this series, in the management of newly diagnosed cases of APL, is associated with responses comparable with conventional chemotherapy regimens, and has minimal toxicity and can be administered on an outpatient basis after remission induction.

Antitumor activity and mechanism of action of the iron chelator, Dp44mT, against leukemic cells

It is shown that Dp44mT had broad activity, inducing apoptosis in several types of acute leukemia and also multiple myeloma cell lines, and a reduction in the mitochondrial trans‐membrane potential and caspase‐3 activation could be involved in the mechanism of apoptosis.

Protein Kinase Inhibitors as Therapeutic Drugs in AML: Advances and Challenges

A brief summary of protein kinase inhibitors investigated in AML thus far, mainly including tyrosine protein Kinase inhibitors and serine/threonine kinase inhibitor is provided.



New Strategies for the Treatment of Acute Myelogenous Leukemia: Differentiation Induction—Present Use and Future Possibilities

It seems unlikely that the morphology‐based French‐American‐British classification alone can be used to identify new subsets of AML patients with special therapeutic requirements, and future studies on differentiation induction in AML should focus on the identification of therapeutic agents with more predictable effects.

Retinoic Acid and Arsenic Synergize to Eradicate Leukemic Cells in a Mouse Model of Acute Promyelocytic Leukemia

Using syngenic grafts of leukemic blasts from PML/RARα transgenic mice as a model for APL, it is demonstrated that arsenic induces apoptosis and modest differentiation, and prolongs mouse survival, and combining arsenic with RA accelerates tumor regression through enhanced differentiation and apoptosis.

All trans retinoic acid in acute promyelocytic leukemia

Overall, more than 90% of patients with newly diagnosed APL can achieve CR and about 75% can be cured by the combination of ATRA and chemotherapy, and it is suggested that maintenance treatment with ATRA, and possibly in combination with low-dose chemotherapy, can further reduce the incidence of relapse.

Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk.

The data show that a strong synergy exists between a low concentration of As(2)O(3) and the cyclic adenosine monophosphate (cAMP) analogue, 8-CPT-cAMP, in fully inducing differentiation of NB4, NB4-R1, and fresh APL cells, which support the existence of a novel signaling cross-talk for APL maturation.

Cotylenin A--A Plant Growth Regulator as a Differentiation-inducing Agent Against Myeloid Leukemia

  • Y. Honma
  • Biology, Medicine
    Leukemia & lymphoma
  • 2002
Cotylenin A, a plant growth regulator, is a potent and novel inducer of the monocytic differentiation of human myeloid leukemia cell lines and leukemia cells freshly isolated from AML patients.

All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results.

The study confirms the major efficacy of all-trans RA in M3, even in relapsing patients, and shows that complete remissions were obtained without bone marrow (BM) hypoplasia and by a differentiation process.

Increased sensitivity of acute myeloid leukemias to lovastatin-induced apoptosis: A potential therapeutic approach.

The evaluation of HMG-CoA reductase inhibitors as a therapeutic approach in the treatment of acute myeloid leukemia is suggested because of the increased sensitivity of neuroblastoma cells to lovastatin-induced apoptosis.