Targeted Therapy for Leukemia

Targeted Therapy for Leukemia: Introduction

Research conducted over the last two decades has yielded a detailed understanding of the molecular lesions that contribute to the malignant transformation of hematopoietic stem cells and committed progenitors into the various forms of acute and chronic leukemia. Although our understanding of the molecular pathology of leukemia remains incomplete, the information gained to date has had a profound impact on the way these malignancies are both diagnosed and monitored during therapy. More recently, targeted therapies have been developed against some of the identified genetic lesions. These therapies have led to significant improvements in patient outcomes while simultaneously decreasing therapy-related toxicity.

Targeted Therapy for Leukemia: Acute Lymphocytic Leukemia

Philadelphia chromosome (Ph)/BCR/ABL-positive acute lymphoblastic leukemia is the most common genetic abnormality associated with adult acute lymphocytic leukemia and has been shown to confer the worst prognosis to both children and adults. BCR–ABL tyrosine kinase inhibitor (TKI) become the main treatment of targeted therapy of acute lymphocytic leukemia

Targeted Therapy for Leukemia: Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The cancer (leukemia) cells start in the bone marrow but then go into the blood. Targeted therapy attacks one or more specific targets on or in cancer cells. The most common targets are BTK, PI3K and BCL-2.

Targeted Therapy for Leukemia: Chronic Myeloid Leukemia

The Philadelphia chromosome (Ph), t(9;22), is the cytogenetic hallmark of chronic myeloid leukemia, this balanced translocation results in the creation of a chimeric BCR-ABL gene that expressesa n 8.5-kb hybrid mRNA transcript and a 210-kD fusion protein. The BCR-ABL gene acted like the gas pedal in a car stuck in the "on" position, fueling the excess growth of white blood cells in chronic myeloid leukemia. With the target identified, a drug discovery program was started, aimed at developing a drug to shut down the activity of BCR-ABL.

Targeted Therapy for Leukemia: Acute Myeloid Leukemia

Traditional therapy for acute myeloid leukemia (AML) relies on conventional DNA-targeted chemotherapy, such as cytarabine plus either daunorubicin or idarubicin. They work by targeting acute myeloid leukemia blasts more than normal cells to produce remission, and are highly cytotoxic. It is increasingly clear that many of these classical therapies cause genetic damage to surviving leukemia cells, which contributes to relapse via the selection of resistant clones. With the discovery of novel tumor-associated mutations and their protein antigens, and the expanding insights into the mechanisms of epigenetic gene regulation and the functions of oncogenic kinases, development of nongenotoxic, “more targeted” therapy with monoclonal antibodies or other inhibitors is being rapidly explored.

Targeted Therapy for Leukemia: Reference

Downing J R. Targeted therapy in leukemia[J]. Modern Pathology, 2008, 21: S2-S7.
Leoni V et al. Tyrosine kinase inhibitors in BCR-ABL positive acute lymphoblastic leukemia[J]. Haematologica, 2015, 100(3): 295.
Woyach JA, et al. Bruton’s tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). Blood. 2014;123(8):1207-1213.
Bedi A et al. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia[J]. Blood, 1994, 83(8): 2038-2044.
Sawyers C L. Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia[J]. Cancer cell, 2002, 1(5): 413-415.

Targeted Therapy
What is Targeted Therapy
Targeted Therapy: Targets
Targeted Therapy for Cancer
Targeted Therapy for Kidney Cancer
Targeted Therapy for Liver Cancer
Colorectal Cancer Targeted Therapy
What is Targeted Therapy for Cancer
Targeted Therapy for Leukemia+
- Targeted Therapy for Acute Lymphocytic Leukemia
- Targeted Therapy for Chronic Lymphocytic Leukemia
- Targeted Therapy for Chronic Myeloid Leukemia
- Targeted Therapy for Acute Myeloid Leukemia
Targeted Therapy for Pancreatic Cancer
Prostate Cancer Targeted Therapy
Targeted Therapy for Ovarian Cancer
Melanoma Targeted Therapy
Targeted Therapy for Lung Cancer+
- Non-Small Cell Lung Cancer (NSCLC) Targeted Therapy
- Small Cell Lung Cancer Targeted Therapy
- EGFR Targeted Therapy Lung Cancer
Targeted Therapy for Breast Cancer+
- Targeted Therapy for Hormone Receptor Positive Breast Cancer
- Targeted Therapy for HER2 Positive Breast Cancer
- Targeted Therapy for Triple-Negative Breast Cancer
- What is Targeted Therapy for Breast Cancer
EGFR Targeted Therapy
HER2 Targeted Therapy
VEGF Targeted Therapy
BRAF Targeted Therapy
ALK Targeted Therapy
Immune Checkpoint Targeted Therapy
Targeted Therapy Drugs
The Differences between Chemotherapy and Targeted Therapy
Side Effects of Targeted Therapy
Oral Targeted Therapy
Targeted Therapy Resistance
How does Targeted Therapy Work