The LL-100 Cell Lines Panel: Tool for Molecular Leukemia–Lymphoma Research

Abstract

Certified cell line models provide ideal experimental platforms to answer countless scientific questions. The LL-100 panel is a cohort of cell lines that are broadly representative of all leukemia–lymphoma entities (including multiple myeloma and related diseases), rigorously authenticated and validated, and comprehensively annotated. The process of the assembly of the LL-100 panel was based on evidence and experience. To expand the genetic characterization across all LL-100 cell lines, we performed whole-exome sequencing and RNA sequencing. Here, we describe the conception of the panel and showcase some exemplary applications with a focus on cancer genomics. Due diligence was paid to exclude cross-contaminated and non-representative cell lines. As the LL-100 cell lines are so well characterized and readily available, the panel will be a valuable resource for identifying cell lines with mutations in cancer genes, providing superior model systems. The data also add to the current knowledge of the molecular pathogenesis of leukemia–lymphoma. Additional efforts to expand the breadth of available high-quality cell lines are clearly warranted.

Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition

“…Therefore, we established a method that matches the manner in which chemotherapy is administered to patients [ 6 ]. NALM-6 is highly sensitive to GC, and it is one of the 5 pre-B-ALL cell lines in 100 authenticated leukemia-lymphoma cell lines [ 20 , 21 ]. Meanwhile, NALM-6 was widely used in the researches on ALL and was recommended as a classic/reference cell line of BCP-ALL [ 21 ].…”

Induced Pluripotent Stem Cells to Model Juvenile Myelomonocytic Leukemia: New Perspectives for Preclinical Research

“…At least, it is possible to maintain undifferentiated JMML cells for approximately 2 weeks in medium supplemented with stem cell factor, Fms-like tyrosine kinase 3 ligand, thrombopoietin (TPO), and interleukin-6, which is sufficient for viral transduction and reprogramming (unpublished own observations). The difficulties are illustrated by the fact that not a single JMML cell line is included in a repertoire of 100+ leukemia cell lines curated in a large academic collection of microorganisms and cell cultures [ 39 ]. Traditionally, it is seen as an advantage of immortalized cell lines that they can be characterized and standardized thoroughly, facilitating the comparison of discoveries made in different labs and enhancing interaction between researchers.…”

Leukemia Cell Lines: In Vitro Models for the Study of Chronic Neutrophilic Leukemia

“…Though data are evolving in this small field, speedier improvement of therapeutic interventions has been hampered by the limited body of knowledge of genetic and cellular underpinnings which, in part, also owes to the lack of representative in vitro cell models. Hence, it appears essential to establish a leukemia cell line model which replicates the in vivo situation [20][21][22]. Furthermore, it is preferable to use cell lines with particular genomic aberrations as proxies for biological features prevailing in the in vivo space.…”

“…Previously, a pair of cell lines was established from a patient with CNL, albeit at different time points during disease progression [22,23]. These cell lines were designated as CNLBC-1 and MOLM-20.…”

“…, CSF3R T618I, EZH2 I146T, NRAS G12D, SETBP1 D868N (EZH2 mutation is homozygous, all other mutations are heterozygous) ASXL1 Y591*, CSF3R T618I, EZH2 I146T, NRAS G12D, SETBP1 D868N (EZH2 mutation is homozygous, all other mutations are heterozygous) Immunoprofile T/NK: CD2−, CD3−, CD4+, CD5−, CD7−, CD10−, CD56+, CD57− B: CD10−, CD19−, CD20−, CD22−, CD79a− MyMon: CD13+, CD14+, CD33+, MPO+ EryMeg: CD41−, CD61− other: CD34+, HLA-DR−, TdT− T/NK: CD3−, CD4+, CD7−, CD56+ B: CD10−, CD19−, CD20−, smIg− MyMon: CD13+, CD14(+), CD15+, CD33+, CD68+, MPO+ EryMeg: CD41− other: CD34+, CD45+, HLA-DR−, TdT− Publication ref. [23]refs [22,24]. …”