Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia (ALL) is a heterogeneous disease with various subtypes, each having distinct genetic and molecular features. Our company has extensive experience providing drug and treatment development services for ALL. Our personalized therapy development strategies are tailored to each client's unique needs.
Introduction to ALL
Acute lymphoblastic leukemia (ALL) is a type of cancer that affects the blood and bone marrow. It is characterized by the uncontrolled proliferation of immature lymphoid cells, called lymphoblasts. The disease arises due to genetic alterations in the lymphoid progenitor cells, leading to the disruption of normal blood cell development. The average person's lifetime risk of developing ALL is very rare, about 1 in 1000. Most cases of acute lymphoblastic leukemia occur in children, but mortality is higher in adults.
Pathogenesis of ALL
The pathogenesis of ALL can result from chromosomal translocations, gene mutations, or epigenetic modifications. For example, chromosomal translocations involving the MLL gene (Mixed-Lineage Leukaemia) are frequently observed in infant and pediatric ALL. The MLL gene fusion partners, such as AF4, AF9, or ENL, result in the aberrant expression of oncogenic fusion proteins. These fusion proteins disrupt normal gene expression patterns and contribute to leukemogenesis.
Diagnostics Development of ALL
One notable diagnostic development is the use of flow cytometry and immunophenotyping to characterize the surface markers expressed on leukemia cells. This technique allows for the identification of specific lymphoblast populations and their maturation stages. Additionally, molecular genetic tests, such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), can detect chromosomal abnormalities and gene mutations associated with ALL subtypes.
Fig.1 Targeted therapies in ALL. (Salvaris Ross, et al., 2021)Therapeutics Development of ALL
- Targets of ALL Therapy Development
CXCR4/CXCL12
One important target is the disruption of the CXCR4/CXCL12 axis. In the bone marrow microenvironment, ALL cells interact with mesenchymal stromal cells (MSCs) through the CXCR4 receptor. Inhibiting this interaction using CXCR4 inhibitors, such as plerixafor and BL-8040, has shown promising results in preclinical and early-phase clinical trials.
Epigenetic Regulators
Another target is the epigenetic regulators involved in ALL pathogenesis. Histone deacetylase (HDAC) inhibitors and inhibitors of bromodomain and extra-terminal motif (BET) proteins have demonstrated efficacy in preclinical models. These inhibitors modulate gene expression and disrupt the activation of oncogenes, such as MYC.
- Types of ALL Therapy Development
Targeted Therapies
Targeted therapies, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have revolutionized the treatment of certain ALL subtypes. For example, the use of TKIs, like imatinib, has shown promising results in Philadelphia chromosome-positive (Ph+) ALL. Monoclonal antibodies, such as blinatumomab, target specific surface antigens on leukemia cells, facilitating immune-mediated killing.
Immunotherapy
Immunotherapy has emerged as a promising approach for the treatment of acute lymphoblastic leukemia (ALL). One specific immunotherapy technique that has shown great potential is chimeric antigen receptor (CAR) T-cell therapy. CARs are genetic constructs designed to recognize specific cell surface markers, and in the case of ALL, they are designed to target the CD19 molecule found on B-cells.
Our Services
Our company is a pioneer in ALL research platforms and technologies, using flow cytometry and molecular biology to help you develop ALL therapies. Our services transcend the realm of ordinary diagnostics, propelling us into the stratosphere of accurate diagnosis and classification of ALL subtypes.
Platforms of ALL Therapy Development
Rare disease model studies, a realm inhabited by only the bravest souls, are our playground. We fearlessly tread where others dare not venture, unraveling the mysteries of ALL with a finesse that defies comprehension. Drug safety evaluation and pharmacokinetic analysis are our specialties. Our unparalleled skills ensure that all services are completed in a timely and efficient manner.
Animal Models of ALL
- Chemically induced leukemia cell lines (L1210, P388, P1534) derived models
- Transgenic ALL animal models (Tet ON/OFF system)
- Zebrafish genetic engineering models
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Salvaris, Ross, and Pasquale Luke Fedele. "Targeted therapy in acute lymphoblastic leukaemia." Journal of Personalized Medicine 11.8 (2021): 715.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.