Chromosome Analysis, Hematologic Disorders, Bone Marrow
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Chromosomal abnormalities play a central role in the pathogenesis, diagnosis, and treatment monitoring of many hematologic disorders. Cytogenetic studies on bone marrow may be helpful in many malignant hematologic disorders as the observation of a chromosomally abnormal clone may be consistent with a neoplastic process.
Certain chromosome abnormalities may help classify a malignancy. As examples, the Philadelphia (Ph) chromosome, also referred to as t(9;22)(q34;q11.2), is usually indicative of chronic myeloid leukemia (CML) or acute leukemia; t(8;21)(q22;q22) defines a specific subset of patients with acute myeloid leukemia; and t(8;14)(q24.1;q32) is associated with Burkitt lymphoma.
Cytogenetic studies are also used to monitor patients with hematologic neoplasia and may identify disease progression, such as the onset of blast crisis in CML, which is often characterized by trisomy 8, isochromosome 17q, and multiple Ph chromosomes.
Conventional chromosome studies of B-cell disorders are not always successful because B lymphocytes do not proliferate well in cell culture. The agent CpG 7909 (CpG) is a synthetic oligodeoxynucleotide that binds to the Toll-like receptor 9 (TLR9) present on B cells, causing B-cell activation. In the laboratory setting, CpG may be used as a mitogen to stimulate B cells in patient specimens, thus allowing identification of chromosome abnormalities. CpG stimulation reveals an abnormal karyotype in approximately 80% of patients with chronic lymphocytic leukemia, and the karyotype is complex in 20% to 25% of cases. Several studies have reported that increased genetic complexity revealed by CpG-stimulated chromosome studies confers a less favorable time to first treatment, treatment response, and overall survival.
See Diagnosis and Monitoring of Multiple Myeloma in Publications.
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
To insure the best interpretation, it is important to provide some clinical information to verify the appropriate type of cytogenetic study is performed.
The following factors are important when interpreting the results:
-Although the presence of an abnormal clone usually indicates a malignant neoplastic process, in rare situations, the clone may reflect a benign condition.
-The absence of an abnormal clone may be the result of specimen collection from a site that is not involved in the neoplasm or may indicate that the disorder is caused by submicroscopic abnormalities that cannot be identified by chromosome analysis.
-On rare occasions, the presence of an abnormality may be associated with a congenital abnormality that is not related to a malignant neoplastic process. Follow-up with a medical genetics consultation is recommended.
-On occasion, bone marrow chromosome studies are unsuccessful. If clinical information has been provided, we may have a fluorescence in situ hybridization (FISH) study option that could be performed.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
In some cases, fluorescence in situ hybridization (FISH) studies may detect some disorders better than conventional chromosome studies:
-For plasma cell proliferative disorders (PCPDs) such as multiple myeloma, FISH studies will detect chromosome anomalies with prognostic significance much more often than conventional chromosome studies. We suggest FPCPD / Plasma Cell Proliferative Disorder (PCPD), FISH.
-Excessive transport time
-Insufficient bone marrow specimen
-Not processing the bone marrow as indicated before shipping the specimen
-Not sending the first aspirate from the patient's bone marrow draw
-Abnormalities missed due to sampling error
-Subtle structural chromosome abnormalities may be missed occasionally
-Neoplastic cells not dividing
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
46,XX or 46,XY. No apparent chromosome abnormality.
An interpretative report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Dewald GW, Ketterling RP, Wyatt WA, Stupca PJ: Cytogenetic studies in neoplastic hematologic disorders. In Clinical Laboratory Medicine. Second edition. Edited by KD McClatchey. Baltimore, Williams and Wilkens, 2002, pp 658-685
2. Rigolin GM, Cibien F, Martinelli S, et al: Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiological parameters. Blood 2012 Mar 8;119(10):2310-2313