Table 1.

Characteristics of validated molecular classes as defined by unsupervised hierarchical clustering

Molecular subtype	%of newly diagnosed patientsa	Genetic characteristics	Characteristic genes elevated in class	Risk	Features
MS(MMSET)	17	t(4;14)	FGFR3, MMSET CCND2, IL6R	High	Overexpression MMSET and FGFR3’ FGFR3 not evident in ∼30%; bone disease is rare
MF(MAF/MAFB)	6	t(14;16) or t(14;20)	MAF or MAFB CCND2, IL6R	High/Moderate	Elevated expression of CCND2; bone disease rare; low DKK1; High NF-kB signature; low TNF-a induced gene TNFAIP8.
CD-1 (CCND1 or CCND3)	6	t(11;14) or t(6;14)	CCND1 or CCND3	Low	Few cases express CCND2 in absence of CCND1 or CCND3; can have high DKK1
CD-2 (CCND1 or CCND3) with CD20 expression	12	t(11;14) or t(6;14)	CCND1 or CCND3, CD20, VPREB3	Low	Few cases express CCND2 in absence of CCND1 or CCND3
HY (HYperdiploid)	31	Typical trisomies +3, +5, +7, +9, +11, +15, +19;	GNG11, DKK1 FRZB	Moderate	Low-ectopic expression of CCND1; del13 and gain of 1q are rare; high expression of interferon-induced genes
LB (Low Bone disease)	12	Typical HY trisomies; exception is frequent del13, gain of 1q, rare gain of 11	CCND2, CST6 ARHE, IL6R	Low	Expression of CCND2; low level DKK1 FRZB,CCR2 HIF1A, SMAD1; low expression of interferon-induced genes
PR (PRoliferation)	10	Made up of all subgroups	CCNB1, CCNB2, PCNA, MKI67 TOP2A, TYMS	High	Overexpression of 1q genes; evolves from other groups

^aApproximately 13% of newly diagnosed cases were not classified. Unclassified samples typically derived from bone-marrow aspirates containing low-bone marrow plasmacytosis. This so-called MY subgroup exhibits superior survival relative to other groups. CD138-purified cells from these cases have GEP of signatures consistent with contamination of preparations with the myeloid, T-cell, B-cell, and plasma-cell lineages. Group consists of all molecular classes described above as spikes and class-specific GEP features are evident in most. Bold and underlined values indicates the source of abbreviations.