Table 2.

The LL-100 Panel: Selected Key Genetic Features and Unique Characteristics.

Entity 1	Cell Line 2	Clinical Data (Diagnosis, Age, Disease Status) 3	Cytogenetics 4	Genomic Landscape 5	Unique Distinction 6
BCP-ALL	697 KOPN-8 NALM-6 REH SEM	pre B-ALL, child, at relapse pre B-ALL, infant, n.r. pre B-ALL, adolescent, at relapse pre B-ALL, adolescent, at relapse pre B-ALL, child, at relapse	t(1;9)(q23;p13) t(11;19)(q23;p13) t(5;12)(q33;p13) t(4;12;21;16)(q32;p13;q22;q24) t(4;11)(q11;q24)	TCF3-PBX1 KMT2A-MLLT1 MSH2 del ETV6-RUNX1, RUNX1-PRDM7 KMT2A-AFF1	reference cell line classic/reference cell line classic/reference cell line
B-NHL: Burkitt/B-ALL	BJAB DAUDI RAJI RAMOS VAL	African Burkitt, child, terminal African Burkitt, adolescent, n.r. African Burkitt, child, n.r. American Burkitt, child, n.r. B-ALL, adult, n.r.	t(11;17)(q23;q23) t(8;14)(q24;q32) t(8;14)(q24;q32) t(8;14)(q24;q32) t(8;14;18)(q24;q32)	KMT2A-CLTC IGH-MYC IGH-MYC IGH-MYC MYC-IGH-BCL2, r	EBV−, classic cell line EBV+, reference cell line EBV+, reference cell line triple-hit B-NHL cell line
B-NHL: CLL/PLL	HG-3 JVM-3 JVM-13 MEC-1 PGA-1	B-CLL, adult, at diagnosis B-PLL, adult, at diagnosis B-PLL, adult, at diagnosis B-CLL, adult, at diagnosis B-CLL, adult, at diagnosis	del(13)(q12q32) trisomy 12, del(13)	R3HCC1L-HTRA1	EBV+ EBV+ EBV+ EBV+ EBV+
B-NHL: DLBCL ABC	NU-DHL-1 OCI-LY3 RI-1 U-2932 U-2946	DLBCL, adult, n.r. DLBCL, adult, at relapse B-NHL, adult, terminal DLBCL, young adult, terminal DLBCL, adult, terminal	t(3;8)(p25;q24), t(14;18) t(14;19)(q32;q13) t(4;8)(q22;q24) t(8;14)(q24;q32) t(8;14)(q24;q32)	IGH-BCL2, MYC r IGH-SPIB, MYD88 mut BCL2 amp, MYC r BCL2 amp IGH-MYC	double-hit B-NHL cell line double-hit B-NHL cell line 2 distinct subclones
B-NHL: DLBCL GCB	DOHH-2 OCI-LY7 OCI-LY19 SU-DHL-4 SU-DHL-6 WSU-DLCL2	B-NHL, adult, refractory DLBCL, adult, at relapse DLBCL, young adult, at relapse DLBCL, adult, n.r. DLBCL, adult, n.r. DLBCL, adult, at relapse	t(8;14;18)(q24;q32;q21) t(8;14)(q24;q32) r(8), t(14;18)(q32;q21) t(14;18)(q32;q21) t(1;3)(q42;q21), t(14;18)(q32;q21) t(3;8)(q27;q24), t(14;18)(q32;q21)	IGH-MYC, IGH-BCL2 IGH-MYC IGH-BCL2, MYC r IGH-BCL2, BCL6 r, MYC r, EZH2 mut IGH-BCL2, BCL6 r, EZH2 mut IGH-BCL2, MYC r, EZH2 mut	double-hit B-NHL cell line double-hit B-NHL cell line triple-hit B-NHL cell line double-hit B-NHL cell line triple-hit B-NHL cell line
B-NHL: HCL	BONNA-12 HAIR-M HC-1	HCL, adult, at diagnosis HCL, adult, terminal HCL, adult, at diagnosis		IGH-TCL1A	EBV+ EBV+ EBV+
B-NHL: MCL	GRANTA-519 JEKO-1 JVM-2 MINO REC-1	MCL, adult, refractory MCL, adult, leukemic conversion MCL, adult, at diagnosis MCL, adult, terminal MCL, adult, terminal	t(11;14)(q13;q32) t(11;14)(q13;q32) t(11;14)(q13;q32) t(11;14)(q13;q32) t(11;14)(q13;q32)	IGH-CCND1 IGH-CCND1 IGH-CCND1 IGH-CCND1 IGH-CCND1	EBV+, reference cell line EBV+, reference cell line
B-NHL: PEL	BC-3 BCBL-1 CRO-AP2 CRO-AP5	Non-AIDS PEL, adult, at diagnosis AIDS PEL, adult, n.r. AIDS PEL, adult, at diagnosis AIDS PEL, adult, terminal		BCL6 mut BCL6 mut, MYC amp BCL6 mut BCL6 mut	EBV− HHV8+ EBV− HHV8+ HIV− EBV+ HHV8+ HIV− EBV+ HHV8+ HIV−
B-NHL: PMBL	U-2940	DLBCL, adolescent, terminal		biallelic SOCS1 del
Multiple Myeloma / PCL	KMS-12-BM L-363 LP-1 OPM-2 RPMI-8226 U-266	Myeloma, adult, terminal PCL, adult, n.r. Myeloma, adult, terminal Myeloma, adult, terminal Myeloma, adult, at diagnosis Myeloma, adult, terminal	t(11;14)(q13;q32) t(4;14)(p16;q32) t(4;14)(p16;q32)	IGH-CCND1, IGH-MYC NRAS mut, TP53 mut IGH-NSD2 IGH-NSD2 MYC ins, biallelic TRAF3 del PTEN del	classic/reference cell line reference cell line classic/reference cell line classic/reference cell line
Hodgkin Lymphoma	HDLM-2 KM-H2 L-428 L-1236 SUP-HD1	Nodular sclerosis, adult, stage IV Mixed cellularity, adult, stage IV Nodular sclerosis, adult, stage IV Mixed cellularity, adult, stage IV Nodular sclerosis, adult, stage IV		CCND2, JAK2 amp, SOCS1 del CIITA-C15ORF65, BCL6 mut, JAK2 BCL6 mut, EZH2 mut, JAK2 amp biallelic SOCS1 mut, STAT6 amp	reference cell line reference cell line reference cell line
T-ALL / T-Lymphoblastic lymphoma	CCRF-CEM DND-41 HPB-ALL JURKAT MOLT-4 RPMI-8402	ALL, child, terminal ALL, child, n.r. T-ALL, child, at diagnosis ALL, child, at relapse ALL, adolescent, at relapse ALL, adolescent, n.r.	t(5;14)(q35;q32) t(5;14)(q35;q32) del(1)(p32), t(11;14)(p15;q11)	NKX2.5-BCL11B TLX3-BCL11B CBFB-MYLPF, TLX3-BCL11B FBXW7 mut, PTEN del, TP53 mut CDKN2A del, NRAS mut LMO1-TRD, STIL-TAL1	classic/reference cell line classic/reference cell line classic/reference cell line classic/reference cell line
Mature T-malignancy	DERL-7 HH MOTN-1	T-NHL, adult, at progression CTCL, adult, terminal T-LGL, adult, chronic phase	t(7;16)(q11;p13)	CDKN2A del, SLFN13 del FOXK2-TP63 CASP8-ERBB4, TBL1XR1-TP63	rare hepatosplenic T-cell line rare T-LGL cell line
NK malignancy	KHYG-1 NK-92 YT	NK leukemia, adult, at diagnosis LGL-NHL, adult, at diagnosis ALL, adolescent, at relapse		BCL2 cna, MYC cna	EBV+, reference cell line EBV+, reference cell line
ALCL	DEL SR-786 SU-DHL-1 SUP-M2	Mal. histiocytosis, child, at diagnosis NHL, child, n.r. Mal. histiocytosis, child, at diagnosis Mal. histiocytosis, child, refractory	t(2;5;6)(p23;q35;p21) t(2;5)(p23;q35) t(2;5)(p23;q35) t(2;5)(p23;q35)	NPM1-ALK NPM1-ALK NPM1-ALK NPM1-ALK	reference cell line classic/reference cell line
AML myelocytic	EOL-1 HL-60 KASUMI-1 KG-1 NB-4 OCI-AML-3 SKNO-1	Eosinophilic AML, adult, at diagnosis AML M2, adult, at diagnosis AML M2, child, at relapse AML, adult, at relapse AML M3, adult, at relapse AML M4, adult, at diagnosis AML M2, young adult, at relapse	t(8;21(q22;q22) t(15;17)(q22;q11) t(8;21)(q22;q22)	FIP1L1-PDGFRA, KMT2A ptd MYC amp, NRAS amp RUNX1-RUNX1T1, KIT mut FGFR1OP2-FGFR1 PML-RARA DNMT3A mut, NPM1 mut RUNX1-RUNX1T1	only eosinophilic cell line classic/reference cell line reference cell line classic/reference cell line classic/reference cell line NPM1-mutated cell line
AML monocytic	ME-1 MOLM-13 MONOMAC6 MUTZ-3 THP-1 U-937	AML M4eo, adult, at relapse AML M5a, young adult, at relapse AML M5, adult, at relapse AML M4, young adult, at diagnosis AML M5, infant, at relapse “Hist. lymphoma”, adult, terminal	inv(16)(p13q22) ins(11;9(q23;p22p23) t(9;11)(p22;q23) inv(3), t(12;22)(p13;q12) t(9;11)(p22;q23) t(10;11)(p13;q14)	CBFB-MYH11 CBL mut, FLT3 itd, KMT2A-MLLT3 RUNX1-ATP8A2, KMT2A-MLLT3 GATA2-EVI1 CSNK2A1-DDX39B, KMT2A-MLLT3 MLLT10-PICALM	sAML post-MDS reference cell line dendritic differentiation classic/reference cell line classic/reference cell line
AML erythroid	F-36P HEL OCI-M2 TF-1	AML M6, adult, at diagnosis AML M6, adult, at relapse AML M6, adult, n.r. AML M6, adult, at diagnosis		CDKN2A del CDKN2A del, JAK2 mut RUNX1-TSPEAR CBFA2T3-ABHD12	sAML post-MDS reference cell line sAML post-MDS reference cell line
AML megakaryocytic	CMK ELF-153 M-07e MEGAL MKPL-1 UT-7	AML M7, infant, at relapse AML M7, adult, at relapse AML M7, infant, at diagnosis AML M7, child, n.r. AML M7, adult, at diagnosis AML M7, adult, at diagnosis	del(5)(q13q32)	CDKN2A mut, GATA1 mut, JAK3 mut ANO7-DHDH, CREBBP mut SET-NUP214 RBM6-CSF1R biallelic CDKN2A del	Down syndrome post-myelofibrosis reference cell line reference cell line
CML myeloid blast crisis	EM-2 K-562 KCL-22 KU-812 LAMA-84	CML, child, blast crisis CML, adult, blast crisis CML, adult, blast crisis CML, adult, blast crisis CML, young adult, blast crisis	t(9;22)(q34;q11) no Ph-chromosome t(9;22)(q34;q11) t(9;22)(q34;q11) t(9;22)(q34;q11)	BCR-ABL1 e14-a2 BCR-ABL1 e14-a2, NUP214-XKR3 BCR-ABL1 e13-a2, CEBPA/B mut BCR-ABL1 e14-a2 BCR-ABL1 e14-a2	reference cell line classic/reference cell line reference cell line basophilic differentiation reference cell line
CML lymphoid blast crisis	BV-173 CML-T1 NALM-1 TK-6	CML, adult, blast crisis CML, adult, acute phase CML, child, blast crisis CML, adult, blast crisis	t(9;22)(q34;q11) no Ph-chromosome t(9;22)(q34;q11) t(9;22)(q34;q11)	BCR-ABL1 e13-a2, CDKN2A/B del BCR-ABL1 e13-a2 BCR-ABL1 e13-a2 BCR-ABL1 e14-a2, MAPK1-AIF1L,	reference cell line classic/reference cell line
Myeloproliferative Neoplasm	MOLM-20 SET-2	CNL, adult, blast crisis Thrombocythemia, adult, leukemia	t(4;11)(q21;q23) no Ph-chromosome	KMT2A-SEPT11, CSF3R mut JAK2 mut	only CNL cell line rare MPN cell line

Discoveries of cytogenetic changes and gene mutational analyses have identified a spectrum of specific genetic alterations in the cell lines of the LL-100 panel representing a highly informative resource in these fields. Please note that this table is selective and does not provide a comprehensive chromosomal and mutational characterization and is by no means an exhaustive list. ¹ The LL entities for which cell lines were selected are based on the two Revised WHO classifications of myeloid and lymphoid neoplasms [31,32] driving categorization of the cell lines (see also Figure 2). ² All cell lines are available from the DSMZ Cell Lines Bank, a non-profit non-commercial government-owned, public cell line repository (www.dsmz.de). ³ Definition of age strata: infant, 0–1 year; child, 1–14 years; adolescent, 14–19 years; young adult, 20–29 years; adult, > 30 years. ⁴ Examples of relevant cytogenetic alterations are listed, e.g., balanced canonical translocation (t) resulting in chimeric fusions listed in the column to the right or rearrangements deregulating oncogenes, deletion (del), inversion (inv), Philadelphia (Ph) or ring chromosome (r). ⁵ Examples of interesting molecular genetic abnormalities and coding alterations are listed, e.g., fusion gene (X-X), gene with amplification (amp), copy number alteration (cna), deletion (del), insertion (ins), internal tandem duplication (itd), mutation (mut), partial tandem duplication (ptd), or rearranged gene (r). The designation of genes follows the terminology approved by the HUGO Gene Nomenclature Committee (www.genenames.org). Older designations are not itemized. ⁶ Unique features: classic/historically important cell lines; virus infection (EBV, Epstein–Barr virus; HHV4, human herpesvirus 4; HIV, human immunodeficiency virus). Some authors have recommended certain cell lines as being particularly well suited to be used as “reference cell lines” [11,29,30] or as “positive control cell lines” in diagnostic procedures applying standardized cell line-based DNA controls [35,36,37,38,39]. Abbreviations of disease entities: ABC, activated B-cell; AIDS, acquired immunodeficiency syndrome; ALCL, anaplastic large cell lymphoma; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; BCP, B-cell precursor; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; CNL, chronic neutrophilic leukemia; CTCL, cutaneous T-cell lymphoma; DLBCL, diffuse large B-cell lymphoma; GCB, germinal center B-cell; HCL, hairy cell leukemia; LGL, large granular lymphocyte (leukemia); Mal., malignant; MCL, mantle cell lymphoma; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasm; NHL, non-Hodgkin lymphoma; NK, natural killer; n.r., not reported; PCL, plasma cell leukemia; PEL, primary effusion lymphoma; PLL, prolymphocytic leukemia; PMBL, primary mediastinal B-cell lymphoma; sAML, secondary AML.