Philadelphia chromosome

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chromosome

 [kro´mo-sōm]
in animal cells, a structure in the nucleus, containing a linear thread of deoxyribonucleic acid (DNA), which transmits genetic information and is associated with ribonucleic acid and histones. In bacterial genetics, a closed circle of double-stranded DNA that contains the genetic material of the cell and is attached to the cell membrane; the bulk of this material forms a compact bacterial nucleus. adj., adj chromoso´mal.

During cell division the material composing the chromosome is compactly coiled, making it visible with appropriate staining and permitting its movement in the cell with minimal entanglement. Each organism of a species is normally characterized by the same number of chromosomes in its somatic cells, 46 being the number normally present in humans, including 22 pairs of autosomes and the two sex chromosomes (XX or XY), which determine the sex of the organism. (See also heredity.)
Chromosome Analysis. This can be done on fetal cells obtained by amniocentesis or chorionic villus sampling, on lymphocytes from a blood sample, on skin cells from a biopsy, or on cells from products of conception such as an aborted fetus. The cells are then cultured in the laboratory until they divide. Cell division is arrested in mid-metaphase by the drug Colcemid. The chromosomes can be stained by one of several techniques that produce a distinct pattern of light and dark bands along the chromosomes, and each chromosome can be recognized by its size and banding pattern. The chromosomal characteristics of an individual are referred to as the karyotype. It is also possible to make a photomicrograph of a cell nucleus, cut it apart, and rearrange it so that the individual chromosomes are in order and labeled. The autosomes are numbered 1–22, roughly in order of decreasing length. The sex chromosomes are labeled X and Y. Karyotyping is useful in determining the presence of chromosome defects.

Before the chromosomes could be precisely identified they were placed in seven groups: A (chromosomes 1–3), B (4–5), C (6–12 and X), D (13–15), E (16–18), F (19–20), and G (21–22 and Y).
Chromosomal Abnormalities. The prevalence of chromosomal disorders cannot be fully and accurately determined because many of these disorders do not permit full embryonic and fetal development and therefore end in spontaneous abortion. About one in every 100 newborn infants do, however, have a gross demonstrable chromosomal abnormality. A large majority of cytogenetic abnormalities can be identified by cytogenetic analysis either before birth, by means of chorionic villus sampling or amniocentesis, or after birth.

Cytogenetic disorders with visible chromosomal abnormalities are evidenced by either an abnormal number of chromosomes or some alteration in the structure of one or more chromosomes. In the language of the geneticist, trisomy refers to the presence of an additional chromosome that is homologous with one of the existing pairs so that that particular chromosome is present in triplicate. An example of this type of disorder is a form of down syndrome (trisomy 21). Another example is patau's syndrome (trisomy 13), which produces severe anatomical malformations and profound mental retardation.

The term monosomy refers to the absence of one of a pair of homologous chromosomes. Monosomy involving an autosome usually results in the loss of too much genetic information to permit sufficient fetal development for a live birth. Either trisomy or monosomy involving the sex chromosomes yields relatively mild abnormalities.

A condition known as mosaicism results from an error in the distribution of chromosomes between daughter cells during an early embryonic cell division, producing two and sometimes three populations of cells with different chromosome numbers in the same individual. Mosaicism involving the sex chromosomes is not uncommon.

Other abnormal structural changes in the chromosome are consequences of some kind of chromosomal breakage, with either the loss or rearrangement of genetic material. translocation involves the transfer of a segment of one chromosome to another. inversion refers to a change in the sequence of genes along the chromosome, which occurs when there are two breaks in a chromosome and the segment between the breaks is reversed and reattached to the wrong ends. deletion occurs when a portion of a chromosome is lost. An example of this type of chromosomal abnormality is cri du chat syndrome, a deletion in the short arm of chromosome 5, marked by mental retardation and sometimes congenital heart defects. When deletion occurs at both ends of the chromosome, the two damaged ends can unite to form a circle and the rearrangement produces a ring chromosome. isochromosomes form when the centromere divides along the transverse plane rather than the normal long axis of the chromosome so that both arms are identical. All of the previously described structural abnormalities can affect both autosomal and sex chromosomes.

The causes of chromosomal errors are not completely understood. In some conditions such as Down syndrome, late maternal age seems to be a factor. Other factors may include the predisposition of chromosomes to nondisjunction (failure to separate during meiosis), exposure to radiation, and viruses.
homologous c's the chromosomes of a matching pair in the diploid complement that contain alleles of specific genes.
Ph1 chromosome (Philadelphia chromosome) an abnormality of chromosome 22, characterized by the translocation of genetic material from its long arm to chromosome 9, seen in the marrow cells of most patients with chronic myelogenous leukemia.
ring chromosome a chromosome in which both ends have been lost (deletion) and the two broken ends have reunited to form a ring-shaped figure.
sex c's the chromosomes responsible for determination of the sex of the individual that develops from a zygote; in mammals they are an unequal pair, the X and Y chromosomes.
somatic chromosome autosome.
X chromosome the female sex chromosome, being carried by half the male gametes and all female gametes; female diploid cells have two X chromosomes.
Y chromosome the male sex chromosome, being carried by half the male gametes and none of the female gametes; male diploid cells have an X and a Y chromosome.

Phil·a·del·phi·a chro·mo·some (Ph1),

an abnormally shortened chromosome 22, formed by translocation of a portion of the long arm of chromosome 22 to chromosome 9; found in cultured leukocytes of many patients with chronic granulocytic leukemia.

Philadelphia chromosome

(fĭl′ə-dĕl′fē-ə)
n.
An abnormal chromosome formed by a reciprocal translocation between chromosomes 9 and 22, found in the white blood cells of people with chronic myelogenous leukemia and causing abnormal activity of a form of tyrosine kinase.

Philadelphia chromosome (Ph)1

Etymology: Philadelphia, Pennsylvania
a translocation of the long arm of chromosome 22, often seen in the abnormal myeloblasts, erythroblasts, and megakaryoblasts of patients who have chronic myelocytic leukemia.
A small acrocentric chromosome from the distal long—q arm of chromosome 22, transferred to chromosome 9q[t(9;22)(q34;q11)] in 95% of chronic myeloid leukaemia; PC is also present in 3% to 5% of childhood acute lymphocytic leukaemia, for whom the prognosis is poor, and 25% of adults
Origin of PC Pluripotent stem cell, which generates myeloid, erythroid, megakaryocytic and lymphoid lines
Management High-dose chemotherapy, Bone marrow transplantation

Philadelphia chromosome

A small acrocentric chromosome from the distal long–q arm of chromosome 22, transferred to chromosome 9q[t(9;22)(q34;q11)] in 95% of CML; PC is present in 3 to 5% of childhood ALL–for whom prognosis is poor, and 25% of adults Origin of PC Pluripotent stem cell, which generates myeloid, erythroid, megakaryocytic and lymphoid lines Molecular pathology Reciprocal translocation, with juxtaposition of the c-abl gene on chromosome 9 with a gene of unknown function, with a bcr–breakpoint cluster region on chromosome 22; the resulting hybrid abl/bcr gene encodes P210bcr/abl, a phosphoprotein unique to CML that resembles v-abl, as it has disregulated protein-tyrosine kinase activity Management High-dose chemotherapy, BMT. See P210bcr/abl.

Phil·a·del·phi·a chro·mo·some

(fil'ă-del'fē-ă krō'mŏ-sōm)
An abnormal minute chromosome. Formed by a rearrangement of chromosomes 9 and 22; found in cultured leukocytes of many patients with chronic granulocytic leukemia.

Philadelphia chromosome

An acquired chromosomal defect in which the long arm of chromosome 22 is deleted and attached (translocated) to another chromosome, usually number 9. Clones of cells with this defect cause chronic myeloid LEUKAEMIA.

Philadelphia chromosome

An abnormal chromosome that is found in patients with a chronic form of leukemia but not in PV patients.
Mentioned in: Polycythemia Vera

Philadelphia,

city in Pennsylvania.
Philadelphia chromosome - an abnormal minute chromosome formed by a rearrangement of chromosomes 9 and 22.
Philadelphia cocktail - Synonym(s): Rivers cocktail
Philadelphia collar - head and neck orthosis.

Philadelphia chromosome

the 9:22 chromosomal translocation characterisitic of human patients with inherited predilection for chronic myelogenous leukemia.
References in periodicals archive ?
8, 2015 /PRNewswire/ -- Cepheid (Nasdaq: CPHD) today announced the commercial availability outside the United States of Xpert BCR-ABL Ultra, a quantitative measure of BCR-ABL1 mRNA transcripts (types e13a2/b2a2 or e14a2/b3a2) that allows physicians to monitor the effectiveness of therapy in their patients with Chronic Myelogenous Leukemia (CML) with enhanced sensitivity.
Ideally, a standard, presumed invariantly expressed "housekeeping gene" would similarly be assessed by qRT-PCR on the same samples, allowing for not only a measure of BCR-ABL fusion per sample but a ratio of it to an internal standard level.
Novel recent investigations for de novo CML patients have examined the validity of gene expression profiling, genetic polymorphisms, next-generation genomics, multidrug resistance genes (MDR, OCT1), fusion transcripts, and preexisting BCR-ABL kinase domain mutations (34), (35), (36), (37), (38), (39), (40), (41), (42), (43).
Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia.
A higher probability of 3-year PFS and OS was seen in patients achieving ≤ 10% BCR-ABL compared to patients who had >10% BCR-ABL levels at 3 months[sup.
With the advent of imatinib, which specifically targeted the TK activity of the oncogenic proteins encoded by BCR-ABL, the management of CML changed dramatically.
The team tested whether Stat3 and Stat5, acting downstream of Bcr-Abl are critical for leukaemia maintenance and if they could be a alternative target for treatment.
Mutations in the Bcr-Abl tyrosine kinase may account for the development of imatinib resistance.
The company expects to enroll approximately 270 adult patients with advanced CML and ALL leukemias harboring the T315I BCR-ABL mutation.
However, the new drugs bind tightly even after the gene that encodes Bcr-Abl has mutated such that imatinib can no longer bind to the altered protein.
San Diego, CA) announced that it has entered into a license and collaboration agreement with Novartis focused on the development and commercialization of BCR-ABL inhibitors for the treatment of drug resistant Chronic Myelogenous Leukemia (CML).
Referred to as a "magic cancer bullet" because of its efficacy in treating chronic myelogenous leukemia and because patients can take it daily at home, imatinib inhibits the protein tyrosine kinases associated with the oncogene Bcr-Abl.