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Distinct types of diffuse large Distinct types of diffuse large B-cell lymphoma identified B-cell lymphoma identified

by gene expression profilingby gene expression profiling

Author: Ash A. Alizadeh, Michael B. Eisen et al. Source: Nature vol.403, 2000 , pp.503-511Speaker: Shu-Fen Chiou( 邱淑芬 )

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OutlineOutline

MicroarrayIntroductionDesign Experimental resultsConclusions

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Microarray(1/2)Microarray(1/2)

( 圖片來源 : 牛頓雜誌 )

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Microarray(2/2)Microarray(2/2)

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Introduction(1/3)Introduction(1/3)Lymphoma ( 淋巴瘤 )

– Hodgkin’lymphoma– Non Hodgkin’s lymphoma

DLBCL-40% of patients have prolonged survival

CLLFL

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Introduction(2/3)Introduction(2/3)

Immune cell ( 免疫細胞 )– Lymphocyte ( 淋巴球 )

B cell- 製造抗體已抵抗細菌和毒素 T cell- 攻擊已被病毒控制的體細胞或癌細胞

– Monocyte ( 單核白血球 )

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Introduction(3/3)Introduction(3/3)

Lymphocyte ( 淋巴球 )– Resting ( 等待 )– Activation ( 活化 )– Transform ( 轉型 )

plasma cell helper macrophage

– Maturation ( 成熟 )

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Design(1/4)Design(1/4)

Using 128 Lymphchip 18432 genes 96 normal and malignant lymphocyte

– 42 DLBCL (Diffuse Large B-cell Lymphoma)– 11 CLL (Chronic Lymphocytic Leukemia )– 9 FL (Follicular Lymphoma)(CD19+)– 34 other ( 類似正常人 )

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Design(2/4)Design(2/4)

34 other– 2 Germinal Center B (B 細胞生發中心 )– 4 Resting B Cell– 10 Activated B Cell(CD40L,IL-4)– 10 Transformed Cell– 6 Resting /Activated T Cell(CD4+,CD4+I+P)– 2 Lymph Node ( 淋巴結細胞 -B 細胞聚集的

地方 )

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Design(3/4)Design(3/4)No.47

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Design(4/4)Design(4/4)

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ExperimentalExperimental results(1/6) results(1/6)

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ExperimentalExperimental results(2/6) results(2/6)

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ExperimentalExperimental results results(3/6)(3/6)

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ExperimentalExperimental results(4/6) results(4/6)

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ExperimentalExperimental results(5/6) results(5/6)Identifier SubGroup Survival indicator Prognostic

IndexMonths 0 -alive

1=dead NA=Not Available

DLCL-0001 GC B-Like 77.4 0 2DLCL-0002 Activated B-like 3.4 1 3DLCL-0003 GC B-Like 71.3 1 2DLCL-0004 GC B-Like 69.6 0 0DLCL-0005 Activated B-like 51.2 0 1DLCL-0006 Activated B-like 3.2 1 3DLCL-0007 Activated B-like 8.3 1 3DLCL-0008 GC B-Like 102.4 0 1DLCL-0009 GC B-Like 89.8 0 0DLCL-0010 GC B-Like 88.1 0 3DLCL-0011 Activated B-like 27.1 1 4DLCL-0012 GC B-Like 4.1 1 2DLCL-0013 Activated B-like 23.7 1 4DLCL-0014 Activated B-like 59 0 1DLCL-0015 GC B-Like 56.6 0 0DLCL-0016 Activated B-like 15.5 1 4DLCL-0017 Activated B-like 2.4 1 3DLCL-0018 GC B-Like 2.9 1 3DLCL-0020 GC B-Like 80.4 0 1DLCL-0021 Activated B-like 4.6 1 2DLCL-0023 GC B-Like 8.2 1 0DLCL-0024 GC B-Like 129.9 0 1DLCL-0025 Activated B-like 32.5 1 NADLCL-0026 GC B-Like 11.8 1 3DLCL-0027 Activated B-like 5.1 1 3DLCL-0028 Activated B-like 90.2 0 2DLCL-0029 GC B-Like 83.8 0 0DLCL-0030 GC B-Like 71.3 0 0DLCL-0031 Activated B-like 12.3 1 2DLCL-0032 GC B-Like 69.1 0 4DLCL-0033 GC B-Like 68.8 0 2DLCL-0034 GC B-Like 1.3 1 4DLCL-0036 Activated B-like 12.67 1 NADLCL-0037 GC B-Like 72.03 0 1DLCL-0039 Activated B-like 91.33 0 3DLCL-0040 Activated B-like 53.73 0 2DLCL-0041 Activated B-like 31.47 1 2DLCL-0042 Activated B-like 39.60 1 1DLCL-0048 Activated B-like 9.45 1 0DLCL-0049 Activated B-like 22.30 1 2DLCL-0051 GC B-Like NA NA NADLCL-0052 GC B-Like NA NA NA

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ExperimentalExperimental results(6/6) results(6/6)

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ConclusionsConclusions

We identified two molecularly distinct forms of DLBCL:– germinal centre B cells ('germinal centre B-like DLBCL')– activation of peripheral blood B cells ('activated B-like

DLBCL').