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HomeHealth articlesleukemiaWhat Are the Molecular and Genetic Basis of Leukemia?

Genetics and Molecular Basis of Leukemia - Insights Into Pathogenesis

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Leukemia is the abnormal multiplication of immature white blood cells that impair the body's capacity to resist infections and perform typical roles.

Written by

Dr. Kinjal Shah

Medically reviewed by

Dr. Rajesh Gulati

Published At June 19, 2023
Reviewed AtJune 19, 2023


Being a multifactorial disease having a hereditary and environmental component, leukemia is a difficult illness. The processes underlying the onset and progression of leukemia have been extensively studied through molecular and genetic research, which have also helped to identify particular genetic changes linked to certain forms of leukemia. The development of tailored medicines that can primarily target the underlying genetic changes that contribute to the illness depends on understanding the molecular and genetic underpinnings of leukemia. New medicines and strategies will probably develop that will improve outcomes for individuals with this difficult illness as the understanding of the molecular pathways behind leukemia continues to expand. Numerous intricate pathways are involved in the molecular and genetic causes of leukemia, which contribute to the onset and development of the illness. Here is a summary of some of the main molecular and genetic causes of leukemia.

What Is Leukemia?

Leukaemia is a form of cancer that affects the bone marrow and blood, which are the organs in charge of creating the body's blood cells. When white blood cells, which make up the majority of blood cells, begin to multiply and divide excessively, they eventually overcrowd the bone marrow and stop the formation of healthy blood cells. This causes various symptoms, including anemia, infections, weariness, weakness, and bleeding. Leukaemia may come in both acute and chronic forms, and each kind is distinguished from the others by the type of blood cell that is afflicted and the speed at which the malignancy spreads. Chemotherapy, radiation therapy, bone marrow transplantation, and other treatments are frequently used to treat leukemia.

What Are the Genetic and Molecular Factors Involved in Leukemia?

  • Abnormal Chromosomal Structures: One of the most frequent genetic changes seen in leukemia is chromosomal abnormalities. Translocations, deletions, and mutations are only a few examples of the genetic alterations that these anomalies may include. Leukemic cells can proliferate out of control as a result of chromosomal anomalies that interfere with the expression of genes that control cell growth, differentiation, and death.

  • Chromosome Abnormalities: Chromosomal abnormalities such as translocations are particularly prevalent in leukemia. Translocations happen when a piece of one chromosome separates and affixes to another. As a result, fusion genes that encode aberrant proteins with carcinogenic characteristics may develop. For instance, the Philadelphia chromosome (Ph) translocation occurs in around 95 percent of instances of chronic myeloid leukemia (CML). The BCR (binding cassette receptor) gene on chromosome 22 and the antibody-binding protein (ABL) gene on chromosome 9 merge to form the Ph chromosome as a consequence of a reciprocal translocation between these two chromosomes. Having constitutive tyrosine kinase activity, the fusion protein produced by the BCR-ABL gene stimulates cell proliferation and prevents apoptosis, which results in the development of CML.

  • Oncogenes: Oncogenes are genes that, when mutated or overexpressed, can result in cancer. Normal cellular genes manage cell division, differentiation, and growth, but, when they are altered, they can become hyperactive and encourage uncontrolled cell development. Based on how they act, oncogenes can be divided into many distinct types. Apoptosis (programmed cell death), a natural mechanism that rids the body of damaged or diseased cells, is inhibited by some oncogenes, whereas other oncogenes produce proteins that encourage cell growth and proliferation. The RAS gene family is one instance of an oncogene. The RAS genes produce proteins that function in signaling systems that control cell proliferation and differentiation. Overactivation may result from RAS gene mutations. Other examples of oncogenes are BCL2, which promotes cell survival and suppresses apoptosis, and MYC, which controls cell proliferation and differentiation. These genes' mutations or overexpression can aid in the onset and spread of cancer. Targeted medicines that can precisely block oncogene activity have been developed as a result of our growing understanding of the function of oncogenes in cancer. Drugs like Imatinib and Dasatinib, for instance, target the BCR-ABL fusion protein that the BCR-ABL oncogene in chronic myeloid leukemia (CML) produces. Cancer treatment has been revolutionized by targeted treatments, and continuing research keeps finding new therapeutic targets.

  • Cancer-Suppressing Genes: Genes known as tumor suppressors typically stop unchecked cell growth. These genes are susceptible to mutations or deletions that can result in the growth of cancer. TP53 is one illustration of a tumor suppressor gene that frequently develops mutations in leukemia. In response to DNA damage, TP53 encodes a protein that controls cell cycle arrest and apoptosis. About 10 to 20 percent of AML patients include TP53 mutations, which are linked with a poor prognosis. TP53 mutations can cause the protein to stop functioning, which may cause an accumulation of cells with DNA damage and the onset of cancer. A WT1 gene mutation is another illustration of a tumor suppressor gene that commonly develops mutations in leukemia. WT1 encodes a transcription factor involved in the growth and differentiation of blood cells. Around ten percent of AML patients include WT1 mutations, and these cases have a dismal prognosis. Leukaemia may arise as a result of WT1 mutations that cause dysregulation of genes involved in cell survival and proliferation.

  • Epigenetic Changes: Epigenetic alterations are adjustments to the DNA (Deoxyribonucleic acid) molecule or to the histone proteins around which DNA is coiled rather than changes in the DNA sequence itself that affect gene expression. By turning genes on or off or by changing the degree of gene expression, these alterations can affect how genes are expressed. Leukemia formation and progression are known to be significantly influenced by epigenetic changes. One illustration is DNA methylation, which is the process by which the cytosine nucleotide in DNA is given a methyl group. At particular areas of the genome known as CpG islands, which are frequently located close to gene promoters, DNA methylation can take place. Methylation of CpG islands can silence a gene's ability to produce proteins by inhibiting the gene's transcription. DNA methylation is commonly changed in leukemia, which causes aberrant expression of the genes responsible for cell division, growth, and death. For instance, methylation of the CDKN2A gene promoter region, which typically produces a protein that controls cell cycle progression, is linked to lower production of the protein and a worse prognosis in acute lymphoblastic leukemia (ALL).

Because epigenetic changes may be reversed, they are a desirable therapeutic target. In reality, many medications that target epigenetic alterations have previously been licensed for the treatment of leukemia. These include the histone acetylation-targeting pharmaceuticals Vorinostat and Romidepsin, as well as the DNA methylation-targeting therapies Azacitidine and Decitabine. In order to provide more potent treatments for leukemia and other diseases, current research is concentrated on discovering new targets for epigenetic therapy.


The development of specific medicines that explicitly target the underlying abnormalities as a result of understanding the molecular and genetic roots of leukemia has improved patient outcomes and decreased the toxicity of standard chemotherapy. The discovery of novel therapies and, ultimately, a cure for this terrible illness depends on an ongoing study into the genetic and epigenetic processes that contribute to leukemia.

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Dr. Rajesh Gulati
Dr. Rajesh Gulati

Family Physician


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