Molecular studies of chronic myelogenous leukemia using the polymerase chain reaction

Article Abstract:

The Philadelphia chromosome was one of the first chromosomal abnormalities found to be commonly associated with leukemia. This abnormality is a reciprocal translocation between chromosomes 9 and 22, which means that a piece of chromosome 9 has been transferred to chromosome 22, and a piece of 22 has been transferred back to 9. While this translocation may be observed by examining chromosomes under the microscope, it was not until the advent of the techniques of molecular biology that the true significance of the translocation became evident. On chromosome 9 there is a gene, c-abl, which plays a role in cell proliferation under normal circumstances. After the translocation, this gene becomes fused with another gene, bcr (which stands for breakpoint cluster), located on chromosome 22. This fusion results in the manufacture of an abnormal protein, which represents a combination of the normal gene products of the two different genes. It is interesting to note that the portion within the bcr gene where the break takes place may determine the type of leukemia that develops. More than 95 percent of patients with chromic myelogenous leukemia have the Philadelphia chromosome, and in these cases the breakpoint is in the so-called major region of bcr. Virtually all children and about half of adults with acute lymphocytic leukemia are Philadelphia- positive; these patients have the breakpoint in the minor region of bcr. Even within the major and minor regions, the breakpoint for the chromosome translocation may occur at different spots. Dividing the major bcr region into five zones, and using the sensitive polymerase chain reaction (PCR), researchers were able to determine in which zone the breakpoint occurred for 32 patients with chronic myelogenous leukemia. They found that in some cases, different breakpoints still resulted in the same messenger RNA being made for protein manufacture. This suggests that either the breakpoints occur in a part of the gene that does not specify protein structure (an ''intron'') or that after the RNA is transcribed from the DNA, it is spliced in such a way as to eliminate differences. Curiously, in two patients with the Philadelphia chromosome, no breakpoint within the bcr could be found, yet abnormal RNA was being manufactured. The explanation for this is not yet certain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Polymerase chain reaction, Myeloid leukemia, Philadelphia-positive, Philadelphia-positive myeloid leukemia, Myelocytic leukemia

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Clinical significance of CD7-positive stem cell leukemia: a distinct subtype of mixed lineage leukemia

Article Abstract:

Leukemia may result from the malignant proliferation of many types of cells, and this is reflected in the different classifications. As its name implies, nonlymphocytic leukemia involves cells other than lymphocytes, one variant of which is acute megakaryocytic leukemia (AMKL). In this form of leukemia, the disease results from the proliferation of megakaryocytes, the bone marrow cells which under normal circumstances would give rise to the tiny platelet cell fragments in the blood. Little is known about AMKL, however. For many years, recognizing AMKL was difficult, since the appearance of the cells under the microscope was often ambiguous. However, in recent years antibodies have become available that can clearly distinguish AMKL from similar forms of leukemia. It is not surprising, therefore, that the number of reported cases of AMKL has increased in recent years. The majority of these cases have involved adults, and it is now thought that AMKL may account for about 12 percent of all adult cases of acute leukemia. AMKL appears to be rare in children. The authors have treated 82 children with acute leukemia over a seven-year period. Only two of those cases were AMKL. The authors now present the observations made in those cases, which are qualitatively different from the findings in adult cases. In both cases, an abnormality in chromosome 21 was present in the leukemia cells. The body cells of one child were normal, but his leukemic cells contained an isochromosome, a chromosome which has been split the wrong way and in which the two arms are equivalent rather than having a long and short arm as is normal. The other patient had Down's syndrome, and therefore had three copies of chromosome 21 (trisomy 21) in her body cells. Curiously, her leukemic cells contained four copies of chromosome 21 (tetrasomy) rather than the normal two or the three of Down's syndrome. While chromosomal abnormalities are also common among adults with AMKL, they most often involve chromosomes 3, 7, 8, and the so-called Philadelphia chromosome, rather than chromosome 21. (Consumer Summary produced by Reliance Medical Information, Inc.)

Case studies, Childhood leukemia, Leukemia in children, Nonlymphoid leukemia

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Cytogenetics of tumor progression

Article Abstract:

Cancer research has been led to the conclusion that the development of a malignant tumor is a process with many individual steps. Among them is the acquisition of aggressive, invasive, malignant characteristics, a process known as tumor progression. How a tumor becomes more aggressive is the subject of research for the author, a recipient, along with Dr. Janet D. Rowley, of the 1989 Charles S. Mott Prize, sponsored by the General Motors Cancer Research Foundation. Focusing on blood tumors like leukemia, the author showed the relationship between progression and chromosomal changes, and in this paper reviews the field of cytogenetics and tumor progression. The most famous chromosome alteration related to cancer is the Philadelphia chromosome. In many patients with chronic myelogenous leukemia, a small piece of chromosome 9 has become translocated to a specific region of chromosome 22. A piece of 22 was translocated to 9, which made chromosome 22 a bit too small. This translocation, abbreviated t(9,22), results in the so-called Philadelphia chromosome. Recent research in molecular biology has found that this small piece of chromosome 9 is the location of the c-abl gene. This gene, c-abl, is one of a set of genes called proto-oncogenes, which play a normal role in the regulation of cell replication, and can be altered in cancerous cells. Proto-oncogenes are closely related to tumor-causing genes found in some viruses. The relationship of chromosome changes to tumor progression in solid tumors is also reviewed, and speculation is presented as to how knowledge of cytogenetics and chromosomes will combine with knowledge of molecular biology to unravel the intricacies of cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Cancer invasiveness, Human chromosome abnormalities

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