Chromosomes in a cell are visible only when the cell is dividing At metaphase stage chromosomes are fully condensed and easy to see. Metaphase spreads are selected and photographed in order to analyze The chromosomes are then arranged in homologous pairs.
Thehomologous pairs are then placed in order of descending size. The sex chromosomes are placed at the end.A picture of chromosomes arranged in this way is known as a karyotype.
Each chromosome should be individually located. A detailed comparison of banding pattern is mandatory between the two homologues. Telomeres are specially important. To ensure the best interpretation, it is important to provide some clinical information.
A “normal” human carries 23 PAIRS of chromosomes (1 set came from the mother, 1 set came from the father) 22 of these sets are called autosomes (or “self chromosomes”) 1 set are the sex chromosomes A female carries two X chromosomes (XX) A male carries an X chromosome and a Y chromosome (XY) Mazen Zaharna Molecular Biology 1/2009
To label a karyotype correctly, first list the number of chromosomes found in the karyotype. Ex. 46 Secondly, list the type of sex chromosomes found in the karyotype. Ex. XX Lastly, list the any abnormalities at the appropriate chromosome number.
Normal Human Female: 46, XXNormal Human Male: 46, XY
Size Human chromosomes range in length from 51 million to 245 million base pairs. They are numbered from largest to smallest
Position of centromere metacentric submetacentric acrocentric
Banding pattern each chromosome has a unique banding pattern Chromosomal bands are alternating light and dark segments that result from various staining procedures. two strong bands on theP-armThree strong bands near the bottom of the q- arm The band width and the order of bands is characteristic of a particular chromosome - a trained cytogeneticist can identify each chromosome (1,2,3...22, X and Y) by observing its banding pattern under the microscope.
Group A: chromosomes 1,2,3 largest metacentric Group B: chromosomes 4,5 large submetacentric Group C: chromosomes 6,7,8,9,10,11,12 medium submetacentric
Group D: chromosomes 13, 14, 15 medium acrocentric Group E: chromosomes 16, 17, 18 short metacentric or submetacentric Group F: chromosomes 19, 20 short metacentric Group G: chromosomes 21, 22 very short acrocentric Mazen Zaharna Molecular Biology 1/2009
Allows any region to be identified by a descriptive address (chromosome number, arm, region, and band) Standard nomenclature is to include the translocation in one set of parentheses and the breakpoints in a second set of parentheses. Thus, this specific translocation would be denoted as t(9;22)(q34;q11.2).
Polyploidy – extra set of the entire genome. (3n, 4n etc) Aneuploidy – the number of chromosomes is not a multiple of the normal haploid number. Monosomy one member of a chromosome pair is missing, (2n-1) Trisomy one chromosome set consists of 3 copies of a chromosome, (2n+1 Mazen Zaharna Molecular Biology 1/2009
Translocationswhen a portion of a chromosome breaks off and rejoins with another chromosome, a common occurrence in leukemias).InversionsChromosomal inversion (inv) requires two breaks in the same chromosome with rotation of the intervening material. Deletions part of the chromosome has been removed Duplications part of the chromosome is duplicated
Translocation Deletion Inversion Isochromosome Insertion Ring Derivative chromosome chromosome
The malignant cells in many patients with leukemia, lymphoma, or another malignant hematologic disease have acquired clonal chromosomal abnormalities. Some specific cytogenetic abnormalities are closely, and sometimes uniquely, associated with morphologically and clinically distinct subsets of leukemia or lymphoma, as well as with their prognosis.
The marrow chromosomes were more difficult to grow, contracted chromosomes with ill defined morphology Assisting in the diagnosis and classification of certain malignant hematological disorders Evaluation of prognosis in patients with certain malignant hematologic disorders Monitoring effects of treatment Monitoring patients in remission
- 8;14 translocation - 4;11 translocation t(11q23) ALL in infants) - 9;22 translocation - 1;19 translocation in pre-B cell ALL - 12;21 translocation in precursor B ALL - Hyperdiploidy - Hypodiploidy - 9p abnormalities in ALL
12;21 is the most common translocation and pretends a good prognosis. 4;11 is the most common in children under 12 months and pretends a poor prognosis
There are substantial differences between children and adults with ALL in the frequencies of some recurring abnormalities, including the following: The t(9;22) is observed in about 2 to 5 percent of children compared with about 30 percent of adults
The t(12;21), which is detectable only by FISH or polymerase chain reaction (PCR) analysis, is observed in about 25 percent of children with B- lineage leukemia , compared with about 3 percent of adults. A hyperdiploid karyotype is found in 30 to 40 percent of children compared with 2 to 10 percent of adults t(4;11) is present in up to 60 percent of infants younger than 12 months, but is rarely observed in adult ALL patients
certaintranslocations, such as t(4;11) and t(9;22), hyperdiploidy (50 to 60 chromosomes) favorable outcome t(12;21), t(1;19) treatment failure even when using intensive chemotherapy
Report Chromosome analysis of the cultured bone marrow cells reveals an abnormal karyotype with an additional copy of chromosome 8 in all ten cells examined. 07 of these ten cells have in addition an extra copy of chromosome 19. Trisomy 8 is a common finding in myeloid disorders including MDS and MPD, but is not specific for any particular disease type. This result shows evidence clonal evolution.
Report 47,XXdel(6),der(12)t(1;12),+21 There is deletion of long arm of chromosome 6 and an unbalanced translocation between the long arms of chromosome 1 and 12. This has resulted in partial Trisomy for the long arm of chromosome 1 and partial monosomy for the chromosome 6. AML in children with Down Syndrome is recognised as a distinct identity. Both dup(1q) and del(6q) are frequent imbalances in Downs Syndrome cases of AML.
The characteristic abnormality in CML is t(9;22)(q34;q11.2) The classic t(9;22)(q34;q11.2) rearrangement occurs in 90-95% of chronic myelogenous leukemia (CML). Karyotype changes associated with increase of fibers in Ph 1-positive cases of CML were trisomy 8 and 19, +Ph1, t (1; 11), and i (17q). Ph 1-positive CML patients with additional karyotype changes had a significantly shorter survival than Ph 1-positive patients without additional chromosome aberrations.
46XX,t(1;12)(p36;q15),t(9;22)(q34;q11) There is a Philadelphia chromosome. All cells also have a translocation between the short arm of chromosome 1 and the long arm of chromosome 12.
The single most important prognostic factor in AML is cytogenetics, or the chromosomal structure of the leukemic cell. Certain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in acute promyelocytic leukemia) About half of AML patients have "normal" cytogenetics; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment.
t(8;21)(q22;q22) t(15;17)(q22;q12 Inv(16) and t(16;16) Rearrangements of 11q23 t(3;3) and inv(3) t(6;9) t(1;22) Chromosomal gain and loss
FAB subtypes show consistent chromosome changes. t(8;21)(q22;q22 93% belong to the M2 and the remaining 7% are M4 t(15;17)(q22;q12 diagnostic of M3 Inv(16) and t(16;16) Inversion or deletion of chromosome 16 is diagnostic of eosinophilia in association with M4 Rearrangements of 11q23 Deletions of 11q are frequently associated with M5
7 Year-old Girl new AML. Indication :AML unspecified.
46XX,inv(16)(p13q22)/47,+22 Female karyotype with a pericentric inversion of chromosome 16 in all ten cells examined. Six of these cells also have an extra copy of chromosome 22. Inv(16) is most often reported in AML M4 with eosinophilia and is usually associated with a favourable prognosis. Additional abnormalities, such as trisomy 22, can be detected at diagnosis but do not appear to affect the prognosis.
Approximately 80% of individuals with CLL have acquired chromosomal abnormalities within their malignant clone and can be categorized into five prognostic groups accordingly: deletion 13q (median survival, 133 months) deletion 11q (median survival, 79 months) trisomy 12 (median survival, 114 months) normal cytogenetics (median survival, 111 months deletion 17p (median survival, 32 months)
Deletion 13q is found in ~55% of patients, making it the most common cytogenetic abnormality in CLL Deletion 11q is identified in ~18% of CLL patients and is associated with several adverse prognostic factors including extensive lymphadenopathy, unmutated IgHV, advanced disease at diagnosis, poor response to treatment, and shorter progression free survival
Trisomy 12 is found in ~16% of CLL, and normal cytogenetics ~18% of CLL patients As intermediate prognostic indicators Deletion 17p is found in ~7% of CLL patients and confers the highest risk poor prognostic indicator. Deletion 17p is a poor prognostic factor
A complex cytogenetic karyotype can be identified in ~16% of patients and is commonly associated with poor prognostic features Reciprocal chromosome translocations are described but rare in CLL