Approximately 45% to 50% of patients with MM have nonhyperdiploid MMs that include patients with hypodiploid, near diploid, pseudodiploid, or near-tetraploid chromosome numbers (fewer than 48 or more than 74 chromosomes), which are characterized by a high frequency of IGH translocations (>85%). With the exception of t(11;14)(q13;q32), most of the nonhyperdiploid patients have an aggressive disease course characterized by a short time to relapse and limited survival. Table 1 outlines a risk stratification system of patients with MM based upon chromosomal abnormalities. These patients are at risk of acquiring genetic events such as deletion of chromosomes 13 and 14, chromosome 17 abnormalities, as well as 1q amplification and 1p deletion.
Table1. Risk Stratification of Myeloma
Both hyperdiploidy and nonhyperdiploidy are also present in patients with MGUS, suggesting that such abnormalities occur early in the course of disease. More detailed analyses using genome-wide CNAs have revealed numerical aberrations in 98% of MM cases and identified amplification of 1q and deletions of 1p, 12p, 14q, 16q, and 20p to be associated with a poor prognosis, whereas gains of chromosomes 5, 9, 11, 15, and 19 are associated with a more favorable outcome.
Hypodiploid karyotype (<44 chromosomes) in MM accounts for one-fifth of all patients with MM and represents an aggressive sub type. In these patients, abnormalities such as monosomy of chromosomes 13, 14, and 22 as well as deletions for 1p, 12p, 16q, and 17p are common. These genotypes are associated with a poor outcome and disease progression. Hypodiploid chromosomal status is an independent risk factor for a poor survival.
