Acute Promyelocytic Leukemia (APL)
The drug discovery process has a number of challenges coupled with limited throughput and long timelines of drug development penetration from laboratory to clinic, and not fitting general market solutions into every single client circumstance. To aid drug development services for APL, Alfa Cytology aims to develop highly effective therapeutic agents for APL that are tailored to client's requirements.
Overview of Acute Promyelocytic Leukemia (APL)
Its recognition in APL is a specific type of acute myeloid leukemia, recognized in 1957, which encompasses 10-15% of all newly diagnosed acute myeloid leukemias. APL features impaired leukemic cell differentiation and block progression in the promyelocytic stage. The genetic alteration giving rise to APL is chromosomal translocation t(15;17) (q22; q12-21) which juxtaposes the promyelocytic leukemia (PML) gene to the retinoic acid receptor alpha (RARA) gene.
Fig. 1. Acute promyelocytic leukemia milestones. (Yilmaz, M. et al., 2021)
Therapy Development for Acute Promyelocytic Leukemia
APL amounts to about 10-15% of AML cases. About 800 patients are diagnosed in the US each year. There is an abnormal WBC count, low platelets, issues in coagulation, bleeding, and prompt diagnosis/treatment. High ATO response rates were reported in the USA and Europe in the mid-80s, but with the fusion of chemotherapeutic agents, the potential for curable formats began to become apparent.
Approved Therapies
The initial drug used is all-trans-retinoic acid. Here is how we normally do it.
| Therapeutic Strategies | Description |
|---|---|
| ATRA Plus Chemotherapy | ATRA is used against anthracycline-based regimens, which can raise the hope of high survival rates and unfathomable cure rates. A previous handful of emerged studies had hoped their best sequence for ATRA and chemotherapy as randomized treatments in mind with reportedly better outcomes among patients who relapsed. Will the ongoing trials study interleukin ATRA to chemotherapy concurrently or sequentially? |
| ATRA Plus Arsenic Trioxide | Arsenic trioxide shows dose- and time-dependent activity on APL, having weakly understood mechanisms, inducing apoptosis steadily in APL cells and being ineffective for inducing apoptosis in myeloid leukemia cells. In vitro and preclinical studies have demonstrated that syndication with ATRA if used with arsenic trioxide (ATO) provides for significant cellular collaboration between them and plays an important role by modulating for immune apoptosis and/or induce differentiation. |
| ATRA - ATO Plus Gemtuzumab Ozogamicin | Gemtuzumab ozogamicin is a monoclonal antibody conjugated with calicheamicin, which has been investigated as an adjunctive therapy in high-risk APL. Gemtuzumab-ozogamicin monoclonal constituents administer ATRA plus arsenic trioxide for patients mostly elderly, those who won't tolerate it or those who don't have full cardiac function. |
Clinical Trials for Acute Promyelocytic Leukemia
Evidence suggests mutations in the PML protein B2 domain cause altered arsenic. Solely ATO has probable urges clothes on. I will replace the normally existing molecules and whatever putative approaches that are possibly considered for these clinical findings to promote change and do away with ATO resistance and the relapse rate in high-risk APL.
| Drug | Phase | CR Rate |
|---|---|---|
| ATRA + oral ATO | 100% | |
| ATRA + RIF | 100% | |
| ATRA + IV ATO | 94% | |
| ATRA + RIF + MT | 100% |
Resistance to Therapy in Acute Promyelocytic Leukemia
Acute promyelocytic leukemia (APL) is a rare cancer of the blood that is curable but can recur. Thus, the need still exists to develop new therapies. Alfa Cytology provides comprehensive APL therapy development services, including but not limited to the following.
Fig. 2. Mechanism of resistance to arsenic trioxide- all-trans retinoic acid (ATO-ATRA) therapy in APL. (Noguera, N.I. et al., 2019)
Acute promyelocytic leukemia (APL) is a rare blood cancer that is usually curable but may relapse. Therefore, the development of highly effective new therapies is still needed. Alfa Cytology provides comprehensive APL therapy development services, including but not limited to the following.
Alfa Cytology offers specialized technical support for your APL research. Whether you're exploring the mechanisms of the disease or involved in drug development, we are the ideal partner. Contact us to learn more about our services.
References
- Yilmaz, M.; et al. Acute promyelocytic leukemia current treatment algorithms. Blood Cancer Journal. 2021, 11(6): 123.
- Jimenez, J.J.; et al. Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget. 2020, 11(11): 992.
- Noguera, N.I.; et al. Acute promyelocytic leukemia: update on the mechanisms of leukemogenesis, resistance and on innovative treatment strategies. Cancers. 2019, 11(10): 1591.