Abstract
Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Cell Lineage
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DNA-Binding Proteins / genetics*
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Gene Expression Profiling
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Gene Expression Regulation, Leukemic / genetics*
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Genes, Homeobox
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Hematopoietic Stem Cells / metabolism
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Hematopoietic Stem Cells / pathology
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Histone-Lysine N-Methyltransferase
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics
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Humans
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Immunophenotyping
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Leukemia, Myeloid / classification
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Myeloid-Lymphoid Leukemia Protein
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Oligonucleotide Array Sequence Analysis
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Oncogene Proteins, Fusion / biosynthesis
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Oncogene Proteins, Fusion / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / classification*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Proto-Oncogenes*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Transcription Factors*
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Translocation, Genetic*
Substances
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DNA-Binding Proteins
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Homeodomain Proteins
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KMT2A protein, human
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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RNA, Messenger
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RNA, Neoplasm
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Transcription Factors
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Myeloid-Lymphoid Leukemia Protein
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Histone-Lysine N-Methyltransferase