A mechanism for cross-lineage gene rearrangements in B-cell neoplasm

Nihon Ketsueki Gakkai Zasshi : Journal of Japan Haematological Society
|December 1, 1989
PubMed

The organization of immunoglobulin heavy chain (IgH) gene of B precursor cell acute lymphoblastic leukemia (ALL) was examined in order to elucidate the mechanism causing simultaneous TCR gene rearrangements. Study using a 5'D probe lying 20 kb upstream of IgH D region genes was useful to distinguish diversity(D)-joining(J) recombination(DJ) from variable(V)-DJ recombination(VDJ). Indeed, IgH gene structures determined by 5'D study well correlated to those recognized by DJ or VDJ transcripts. IgH gene rearrangements of B precursor cell ALL showed developmentally restricted gene recombination; DJ/DJ genotype in the most immature stage and VDJ/VDJ genotype in the relatively mature stage. B precursor cell ALL with simultaneous rearrangements were frequently found in relatively mature cells, i.e., CD20 expressing cells on their surface. Furthermore, most of such dual genotypic ALL showed that at least one allele of IgH genes was VDJ recombination. This finding suggests that dual genotype was the incidental product by a putative common recombinase during the process of VH gene rearrangements. Moreover, since IgH gene rearrangements of acute unclassified leukemia with dual genotype were DQ52 genotype, which indicates abortive gene rearrangements, it was also thought that dual genotype occurred due to the pluripotentiality of the stem cell.

Related Concept Videos

Crossing Over01:34

Crossing Over

Unlike mitosis, meiosis aims for genetic diversity in its creation of haploid gametes. Dividing germ cells first begin this process in prophase I, where each chromosome—replicated in S phase—is now composed of two sister chromatids (identical copies) joined centrally.
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...
Gene Conversion02:08

Gene Conversion

Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Crossing Over01:30

Crossing Over

Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I, duplicated...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...