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MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct …
In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated ...
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MicroRNA-205 downregulates mixed-lineage-AF4 oncogene …
Myeloid/lymphoid or mixed-lineage AF4 acute lymphoblastic leukemia (MLL-AF4 ALL) is a pediatric leukemia that occurs rarely in adults. MLL-AF4 ALL is typically characterized by the presence of chromosomal translocation (t (4;1l) (q21;q23)), leading to expression of MLL-AF4 fusion protein. Although MLL-AF4 fusion protein triggers a …
Synergistic targeting of FLT3 mutations in AML via combined menin-MLL
The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1 mut) and MLL-rearranged (MLL-r) leukemias.Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the …
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How I treat infant leukemia
A nonbiased RNA interference screen of 243 chromatin-modifying genes identified BRD4 to be required for the maintenance of leukemia in an MLL-AF9 murine model. 68 Potent and selective small-molecule inhibitors of BRD4 binding downregulated characteristic KMT2A-r and MYC target genes and demonstrated in vitro and in vivo …
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Antibody-Dependent Cell-Mediated Cytotoxicity Overcomes …
MLL-rearranged leukemias have a poor response to standard treatments, including chemotherapy and hematopoietic stem cell transplantation.Unfortunately, these leukemia cells often have an NK-resistant phenotype. We found that this resistance could be overcome by antibody-dependent cell-mediated cytotoxicity (ADCC) against specific …
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Drug Repurposing for Targeting Acute Leukemia With KMT2A (MLL…
The treatment failure rates of acute leukemia with rearrangements of the Mixed Lineage Leukemia (MLL) gene highlight the need for novel therapeutic approaches. Taking into consideration the limitations of the current therapies and the advantages of novel strategies for drug discovery, drug repurposing offers valuable opportunities to identify …
The MLL recombinome of acute leukemias in 2017
Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia ...
KMT2A Gene
KMT2A (Lysine Methyltransferase 2A) is a Protein Coding gene. Diseases associated with KMT2A include Wiedemann-Steiner Syndrome and Acute Myeloid Leukemia With T(9;11)(P22;Q23).Among its related pathways are Gene expression (Transcription) and RNA Polymerase I Promoter Opening.Gene Ontology (GO) annotations related to this …
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PROM1 and CTGF Expression in Childhood MLL …
The prognosis of over 90% of infant acute lymphoblastic leukemia (ALL) remains poor because of harboring the mixed-lineage leukemia gene (MLL) fusion. To give insight into the critical coexpressed genes related to the MLL-rearrangement (MLL-R) gene in childhood acute lymphoblastic leukemia, we …
Primary Acute Myeloid Leukemia
Abnormalities involving the MLL ( m yeloid- l ymphoid l eukemia or m ixed l ineage l eukemia) gene at chromosome band 11q23 are found in approximately 5% to 10% of patients with primary AML and ...
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Improved Research Model for Childhood Leukemia
The model closely mimics how this cancer arises and progresses in humans. The overall cure rate of childhood B-cell ALL has improved dramatically in recent decades. But this same success has not extended to children under age 1 with the most common type of infant leukemia, an aggressive ALL subtype known as t (4;11) pro-B ALL or MLL-AF4 …
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miR-9 is an essential oncogenic microRNA …
In the present study, through a large-scale, genomewide miRNA expression profiling assay of 85 human AML cases (including 10 MLL rearranged and 75 others), along with 15 normal controls, we show …
MLL-Rearranged Acute Lymphoblastic Leukemia
doi: 10.1007/s11899-020-00582-5. Acute lymphoblastic leukemia; KMT2A; MLL; Resistance. MLL-r-ALL cells are characterized by relative resistance to corticosteroids (due to Src kinase-induced phosphorylation of annexin A2) and L-asparaginase therapy, but they are sensitive to cytarabine chemotherapy (due to increased levels of hENT1 expression).
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This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which …
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In general, a MLL can result in localised tenderness with discomfort due to the pressure effect of the large volume of serosanguinous fluid within a well-defined space. The most common location over the lateral hip and greater trochanter can make side-lying particularly difficult and painful, resulting in sleep interruption.
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Mucin Neovascularization as a Diagnostic Aid to Distinguish
In 116 cases with sufficient remaining material (42 MC, 16 mDCIS, and 58 MLL), we also assessed mucin neovascularization on CD31 immunostains. On H&E-stained sections, neovascularization of mucin, defined as delicate, thin-walled microvessels in mucin, and unassociated with fibrous septae, was identified significantly more frequently in MC than ...
Systematic Classification of Mixed-Lineage Leukemia Fusion …
Chromosomal translocations of the human mixed-lineage leukemia (MLL) gene have been analyzed for more than 20 yr at the molecular level. So far, we have collected about 80 direct MLL fusions (MLL-X alleles) and about 120 reciprocal MLL fusions (X-MLL alleles). The reason for the higher amount of rec …
Pro-B-cell to pre-B-cell development in B-lineage acute …
Human acute lymphoblastic leukemia (ALL) frequently involves clonal expansion of a CD19 + B-lineage cell at one of several stages of B-cell development.3,9,10 Infant acute leukemia is a malignancy with distinct biologic and clinical features, and 60% to 70% of patients harbor rearrangements of the mixed-lineage leukemia (MLL) gene at …
How I treat mixed-phenotype acute leukemia | Blood
Of 92 patients assessed, 64% presented with cytogenetic abnormalities; CK was the most prevalent aberration found in 24% of patients, followed by Ph + chromosome in 15% (all B-myeloid phenotype) and translocations involving MLL gene at 11q23 in 4.3% of patients. Monosomy 7, polysomy 21, and trisomy 8 were also noted in a significant …