26612 Chromosome Analysis, Hematologic Disorders, Bone Marrow (CHRBM)

​​Karyotype, Bone Marrow​

​Assisting in the diagnosis and classification of certain malignant hematological disorders in bone marrow specimens

Evaluating the prognosis in patients with certain malignant hematologic disorders

Monitoring effects of treatment

Monitoring patients in remission

​NECESSARY INFORMATION

1. A reason for testing should be submitted with each specimen. Mayo labs will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
2. A pathology and/or flow cytometry report may be requested by Mayo labs to optimize testing and aid in interpretation of results.​

Collection Instructions:
1. It is preferable to send the first aspirate from the bone marrow collection.
2. Invert several times to mix bone marrow.

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

​In some cases, fluorescence in situ hybridization (FISH) studies may detect some disorders better than conventional chromosome studies:

-For plasma cell proliferative disorders such as multiple myeloma, FISH studies will detect chromosome anomalies with prognostic significance much more often than conventional chromosome studies. In this situation, PCPDS / Plasma Cell Proliferative Disorder, High-Risk with Reflex Probes, Diagnostic FISH Evaluation, Bone Marrow
 is recommended.

Interfering factors:
Technical:
-Insufficient bone marrow specimen
-Use of an improper anticoagulant or improperly mixing the blood with the anticoagulant
-Clotted bone marrow specimen
-Excessive transport time
-Exposure of the specimen to extreme temperature
-Not processing the bone marrow as indicated before shipping the specimen
-Not sending the first aspirate from the patient's bone marrow collection

Biological:
-Abnormalities missed due to sampling error
-Subtle structural chromosome abnormalities may not be detected by conventional chromosome analysis
-Neoplastic cells not dividing or not present in bone marrow

​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 der(22)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 (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.

​To ensure 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 constitutional 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, there may be a fluorescence in situ hybridization study option that could be performed.