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ML-1 cell line lacks a germline MLL locus
M P Strout1, K Mrózek, K Heinonen
1Division of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Genes, Chromosomes & Cancer
|July 1, 1996
Summary
Acute myeloid leukemia (AML) cell lines lacking a normal MLL gene can still proliferate and differentiate. This study identifies an AML cell line with a deleted MLL allele, demonstrating normal MLL is not essential for cell survival.
Area of Science:
- Molecular Biology
- Hematology
- Genetics
Background:
- Gene rearrangements involving the MLL (mixed lineage leukemia) gene are frequent in acute leukemia.
- Typically, one MLL allele is rearranged, while the other remains in a germline configuration.
Purpose of the Study:
- To characterize a unique acute myeloid leukemia cell line (ML-1) lacking a germline MLL allele.
- To investigate the functional requirement of a normal MLL gene product for leukemic cell survival and differentiation.
Main Methods:
- Karyotypic analysis and molecular cloning of genomic breakpoints.
- DNA sequencing to analyze the precise translocation and insertion events.
- Induction of differentiation in the ML-1 cell line.
Main Results:
- The ML-1 cell line possesses a t(6;11)(q27;q23) translocation, with the remaining MLL allele deleted.
- A 186-bp segment of MLL intron 6 was duplicated, inverted, and inserted into the der(11) chromosome.
- ML-1 cells demonstrated inducibility for granulocyte and macrophage differentiation.
Conclusions:
- A normal MLL gene is not essential for the survival, proliferation, or differentiation of the ML-1 acute myeloid leukemia cell line.
- This finding challenges the absolute requirement of a functional MLL allele in certain leukemic contexts.