Several characteristic genetic changes lead to the creation of a leukemic lymphoblast. These changes include chromosomal translocations, intrachromosomal rearrangements, changes in the number of chromosomes in leukemic cells, and additional mutations in individual genes. Chromosomal translocations involve moving a large region of DNA from one chromosome to another. This move can result in placing a gene from one chromosome that promotes cell division to a more actively transcribed area on another chromosome. The result is a cell that divides more often. An example of this includes the translocation of C-MYC, a gene that encodes a transcription factor that leads to increased cell division, next to the immunoglobulin heavy- or light-chain gene enhancers, leading to increased C-MYC expression and increased cell division. Other large changes in chromosomal structure can result in the placement of two genes directly next to each other. The result is the combination of two usually separate proteins into a new fusion protein. This protein can have a new function that promotes the development of cancer. Examples of this include the ETV6-RUNX1 fusion gene that combines two factors that promote blood cell development and the BCR-ABL1 fusion gene of the Philadelphia chromosome. BCR-ABL1 encodes an always-activated tyrosine kinase that causes frequent cell division. These mutations produce a cell that divides more often, even in the absence of growth factors. Other genetic changes in B-cell ALL include changes to the number of chromosomes within the leukemic cells. Gaining at least five additional chromosomes, called high hyperdiploidy, occurs more commonly. Less often, chromosomes are lost, called hypodiploidy, which is associated with a poorer prognosis. Additional common genetic changes in B-cell ALL involve non-inherited mutations to PAX5 and IKZF1. In T-cell ALL, LYL1, TAL1, TLX1, and TLX3 rearrangements can occur. ALL results when enough of these genetic changes are present in a single lymphoblast. In childhood ALL, for example, one fusion gene translocation is often found along with six to eight other ALL-related genetic changes. The initial leukemic<unk> opies itself into an excessive number of new lymphoblasts, none of which can develop into functioning lymphocytes. These lymphoblasts build up in the bone marrow and may spread to other sites in the body, such as lymph nodes, the mediastinum, the spleen, the testicles, and the brain, leading to the common symptoms of the disease.
Acute lymphoblastic leukemia
Aplastic anemia
Acute myeloid leukemia
Infectious mononucleosis
Prolymphocytic leukemia
Lymphoid leukemia
Myeloid leukemia
Chronic lymphocytic leukemia