As I was struggling to understand the results of Richard's recent cytogenetic studies, I stumbled on a new publication in Mayo Clinic Proceedings that really added to my understanding of the genetic/chromosomal aspects of myeloma. I was able to download the article from here. The complete citation can be found at the end of the post. But I digress.
Richard has had a total of six bone marrow biopsies, five at Mayo. The cytogenetic results of the first four were "normal karyotype XY". The most recent biopsy done in February showed many abnormalities.
A karyotype is a picture of chromosomes. Humans have 46 chromosomes, 23 come from mom and 23 from dad. If you get dad's Y chromosome, you're a boy. If you get dad's X chromosome, you're a girl. The chromosomes contain the genes that are responsible for all of the cellular processes.
Traditional cytogenetics examines dividing cells from the bone marrow for abnormalities. Abnormalities are not apparent in cells that are not dividing. There fore, if there are relatively few dividing cells, few abnormalities will be seen. This explains why abnormal karyotypes are seen in only 18% to 30% of persons with newly diagnosed myeloma.
A newer more sensitive examination reveals chromosomal abnormalities in nearly all persons newly diagnosed with myeloma. The test is called fluorescence in situ hybridization or FISH analysis.
So if chromosomal abnormalities are apparent with conventional cytogenetic testing, then cells are rapidly dividing and the myeloma is very active. A high plasma cell labeling index (PCLI) usually accompanies an abnormal chromosome test. A high PCLI is >1.0%. Richard's was 4.1%. Not good.
As I understand it, the reason for doing the chromosome studies especially at diagnosis is that while most all patients have abnormalities at diagnosis, certain abnormalities have worse predictive survival prognoses than others.
The main types of abnormalities include deletions, translocations, hyperploidy, and hypoploidy. Deletion means that all of part of a chromosome is missing. The chromosome 13 deletion is the most commonly known and is a predictor of decreased survival.
Translocation means that one or more chromosomes are located in the wrong place. Some translocations t(11;14)(q13:q32) predict better survival than others.
Hyperploidy means multiple copies of chromosomes. It is a more favorable predictor of survival than hypoploidy. Hypoploidy means entire chromosomes are missing.
Chromosomal tests are done to identify patients with poorer prognoses that may benefit from more agressive treatments.
For more information and much more detail, download the article.
Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statment Angela Dispenzieri, S. Vincent Rajkumar, Morie A. Gertz, Rafael Fonseca, Martha Q. Lacy, P. Leif Bergasel, Roert A. Kyle, Philip R. Greipp, Thomas E. Witzig, Craig B. Reeder, John A. Lust, Stephen J. Russell, Suzanne R. Hayman, Vivek Roy, Shaji Kumar, Steven R. Zeldenrust, Robert J. Dalton, A. Keith Stewart.Mayo Clin Proc. March 2007;82(3):323-341