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DNA microarray in DLBCL

DNA microarray in DLBCL

DNA microarray in DLBCL

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The New England Journal of Medic<strong>in</strong>elarge subgroups (Fig. 1A). One had a high level ofexpression of the genes characteristic of germ<strong>in</strong>alcenterB-cell–like diffuse large-B-cell lymphoma andnormal germ<strong>in</strong>al-center B cells, another expressedgenes characteristic of activated B-cell–like diffuselarge-B-cell lymphoma and mitogenically activatedblood B cells, and the third, termed type 3 diffuselarge-B-cell lymphoma, did not express either set ofgenes at a high level. The heterogeneity of expressionwith<strong>in</strong> this third subgroup <strong>in</strong>dicates that it mayconsist of more than one type of diffuse large-B-celllymphoma.The subgroups differed substantially with respect totwo recurrent oncogenic events. The t(14;18) translocation<strong>in</strong>volv<strong>in</strong>g the bcl-2 gene and the amplificationof the c-rel locus on chromosome 2p occurred exclusively<strong>in</strong> germ<strong>in</strong>al-center B-cell–like diffuse large-B-celllymphomas (Fig. 1B). These f<strong>in</strong>d<strong>in</strong>gs support the viewthat the various subgroups represent different diseasesthat arise as a result of dist<strong>in</strong>ct mechanisms of malignanttransformation. 3,11The cl<strong>in</strong>ical and pathological features of the threesubgroups are shown <strong>in</strong> Table 1. The most commonhistologic type of diffuse large-B-cell lymphoma —centroblastic monomorphic — was found <strong>in</strong> 66 percentof the germ<strong>in</strong>al-center B-cell–like subgroupbut also <strong>in</strong> 32 percent of the activated B-cell–like subgroupand 27 percent of the type 3 subgroup. Centroblasticpolymorphic and immunoblastic subtypeswere more common <strong>in</strong> activated B-cell–like andtype 3 diffuse large-B-cell lymphomas, but they werealso observed <strong>in</strong> the germ<strong>in</strong>al-center B-cell–like subgroup.Thus, these three subgroups were not strictlyrelated to a specific histologic subtype. With respectto cl<strong>in</strong>ical features, a significantly higher proportionof patients <strong>in</strong> the activated B-cell–like subgroupthan <strong>in</strong> the other two groups were older than 60years of age (P=0.05) and had an ECOG performancestatus of more than 1 (P=0.03), but the tumorsubgroup did not correlate with the risk groups def<strong>in</strong>edon the basis of the <strong>in</strong>ternational prognostic <strong>in</strong>dex(P=0.44).Overall survival after anthracycl<strong>in</strong>e-based chemotherapydiffered significantly among the three subgroups(P1¬ normal 57 56 50 65 0.3Age >60 yr 55 48 58 66 0.05Ann Arbor stage >II 55 53 53 59 0.68No. of extranodal sites >1 20 20 25 15 0.34ECOG performance status >1 22 19 16 33 0.03Risk group 0.44Low (score, 0–1) 37 40 41 29Intermediate (score, 2–3) 49 49 43 51High (score, 4–5) 14 11 15 19Histologic subtypeCentroblastic monomorphic 47 66 27 32

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