ArticleThe Journal of clinical investigation1994
Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes.
Article in The Journal of clinical investigation, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 165 citations in OpenAlex.
- Prognostic factors in infants with acute myeloid leukemia.Leukemia · 2000Trial
- Structure-Based Development of Novel Spiro-Piperidine ASH1L Inhibitors.Journal of medicinal chemistry · 2025Article
- Menin-MLL1 Interaction Small Molecule Inhibitors: A Potential Therapeutic Strategy for Leukemia and Cancers.Molecules (Basel, Switzerland) · 2023Review
- Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity.Nature communications · 2021Article
- Acute Leukemia in Infants.Current oncology reports · 2021Review
- Targeting epigenetic protein-protein interactions with small-molecule inhibitors.Future medicinal chemistry · 2020Review
- Rewiring the Epigenetic Networks inFrontiers in cell and developmental biology · 2019Review
- Facile target validation in an animal model with intracellularly expressed monobodies.Nature chemical biology · 2018Article
- Improved outcome of childhood acute myeloid leukemia in an Eastern European country: Lithuanian experience.European journal of pediatrics · 2017Article
- Molecular targeting in acute myeloid leukemia.Journal of translational medicine · 2017Review
- Symptomatic central nervous system involvement in adult patients with acute myeloid leukemia.Cancer management and research · 2017Article
- The role of HTS in drug discovery at the University of Michigan.Combinatorial chemistry & high throughput screening · 2014Review
- Article
- Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group.International journal of hematology · 2013Article
- MLL gene rearrangements in infant leukemia vary with age at diagnosis and selected demographic factors: a Children's Oncology Group (COG) study.Pediatric blood & cancer · 2012Article
- Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report.Leukemia · 2012Article
- Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia.Nature chemical biology · 2012Article
- Crystal structure of menin reveals binding site for mixed lineage leukemia (MLL) protein.The Journal of biological chemistry · 2011Article
- Epigenetic regulations in hematopoietic Hox code.Oncogene · 2011Review
- Molecular basis of the mixed lineage leukemia-menin interaction: implications for targeting mixed lineage leukemias.The Journal of biological chemistry · 2010Article
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Authors and funding
9 authors at 5 institutions in 1 country.
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Abstract
Cytogenetic studies have previously identified abnormalities of chromosome band 11q23 in many cases of infant acute leukemia. Recent studies by ourselves and others have demonstrated breakpoint clustering in acute leukemias bearing translocations involving 11q23, and a Drosophila trithorax gene homologue (called MLL, HRX, or ALL-1) has been shown to span the 11q23 breakpoints of these translocations. To determine if this gene is affected in infant acute myeloid leukemia (AML), we have analyzed 26 infant AML cases for molecular alterations of this 11q23 gene. 15 out of 26 cases studied (58%) showed rearrangement of the MLL gene at the molecular level, and these rearrangements were clustered within an approximately 11-kb region containing nine exons of this gene. Moreover, 14 of the 15 cases with 11q23 rearrangements (93%) had myelomonocytic or monocytic phenotypes (M4 or M5 FAB subtypes, respectively), both of which are associated with a poor prognosis in childhood AML. In contrast, only 1 of 11 nonrearranged cases had an M4 or M5 phenotype (P = 0.00002). Rearrangement also correlated significantly with hyperleukocytosis (P = 0.02), another clinical parameter associated with poor outcome in this disease. Our results demonstrate that molecular rearrangements of MLL are common in M4 or M5 infant AML, and suggest that alteration of this gene may result in abnormal control of proliferation and differentiation in monocytic progenitor cells.
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