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 ASXL1, Recurrent somatic ASXL1 mutations occur in patients with myelodysplastic syndrome,myeloproliferative neoplasms, and acute myeloid leukemia, and are associated with adverseoutcome. Despite the genetic and clinical data implicating ASXL1 mutations in myeloidmalignancies, the mechanisms of transformation by ASXL1 mutations are not understood. Here,we identify that ASXL1 mutations result in loss of polycomb repressive complex 2 (PRC2)-mediated histone H3 lysine 27 (H3K27) tri-methylation. ASXL1 mutations are loss-of-functionmutations ASXL1 loss results in a genome-wide reduction in H3K27me3 occupancy.ASXL1interacts with the PRC2 complex and is important for PRC2 recruitment. ASXL1 collaborates withco-occurring oncogenes in vivo to promote leukemogenesisCBL,DNMT3A, DNA (cytosine-5-)-methyltransferase 3 alpha. CpG methylation is an epigenetic

modification that is important for embryonic development, imprinting, and X-chromosomeinactivation. Studies in mice have demonstrated that DNA methylation is required for 

mammalian development. This gene encodes a DNA methyltransferase that is thought to functionin de novo methylation, rather than maintenance

methylation. The protein localizes to the cytoplasm and nucleus and its expression isdevelopmentally regulated. Alternative splicing results in multiple transcript variants encodingdifferent isoforms.Plays a role in paternal and maternal imprinting. Required for methylation of 

most imprinted loci in germ cells.(AML,MDS).IDH1 isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-

oxoglutarate. These enzymes belongto two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other 

NADP(+). Fiveisocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate

dehydrogenases, which localize to themitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is

mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein

encoded by this gene is theNADP(+)-dependent isocitrate dehydrogenase found in the cytoplasm and peroxisomes. It

contains the PTS-1 peroxisomaltargeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the

regeneration of NADPH for 

intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, aswell as in peroxisomal

reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. Thecytoplasmic enzyme serves

a significant role in cytoplasmic NADPH production. (provided by RefSeq, Jul 2008)IDH2, Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong

to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five

isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitratedehydrogenases, which localize to the

mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which ismitochondrial and the other 

predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The proteinencoded by this gene is theNADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in

intermediary metabolism andenergy production. This protein may tightly associate or interact with the pyruvate

dehydrogenase complex. (providedby RefSeq, Jul 2008)

JAK2,

MPL,

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NF1,SF3B1, Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene.Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes.SUZ12,TET2 The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes theconversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved inmyelopoiesis, and defects in this gene have been

associated with several myeloproliferative disorders. Two variants encoding different isoformshave been found for this gene. (provided by RefSeq, Mar 2011) Function: Catalyzes theconversion of methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). Plays an important role in

myelopoiesis. The clear function of 5-hydroxymethylcytosine (hmC) is still unclear but it mayinfluence chromatin structure and recruit specific factors or may constitute an intermediatecomponent in cytosine demethylation.BAALC,MN1ERG

ETV6RPS14BIRC3(aka API2)-MALT1

BCL10-FOXP1GPR34miR-145 5q- syndrome

DEKNUP214(CAN)

 A20, ABIN-1/2CARD11TRBMYBMLLMLLT4

ID4HOXABCL11B

PAX5 (PAX5 Location 9p13.2 Protein Lineage-specific transcription factor; recognizes

the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is anynucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors

into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes

and repress genes involved in other lineage commitments. Activates the surface cellreceptor CD19 and repress FLT3. Pax5 physically interacts with the RAG1/RAG2

complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and

induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells

are restored in their function in mature B cells and plasma cells, and PAX5 repressed(Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007)

TAL2NOTCH1TLX1LMO1LMO2CCND2

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MNX1LYL1CEBPDMYCCDKN2AJAK2ZMIZ1

 ABL1MLLT3PICALMEML1MLLT10TRA/DLMO1LMO2TAF15ZNF384TCF3ETV6RUNX1

EWSR1ZNF384OLIG2EZH1EZH2FLT3 FMS-like tyrosine kinase 3 ( FLT3 ) encodes a class III receptortyrosine kinase for the FLT3 ligand and representsthe most commonly mutated gene in patients with acutemyeloid leukemia (AML) identifi ed to date. Mutations inFLT3 most commonly occur as in-frame insertions of duplicatedsequences in the juxtamembrane region (JMD) orin the cytoplasmic tyrosine kinase domain 1 (TKD1), bothof which are referred to as FLT3 internal tandem duplications

( FLT3-ITD s). FLT3-ITD mutations are one of the fewmolecular predictors that are currently clinically utilized inrisk-stratifi cation of patients with AML, as the presence of the FLT3-ITD has consistently been shown to be an adversepredictor of overall survival (OS) and relapse in AML, independentof cytogenetic classifi cation.EVI1 a zinc finger transcriptional regulator that binds to DNA sequences in the promoterregion of target genes and positively or negatively regulates their expression. Anoncogene which plays a role in development, cell proliferation and differentiation. Mayalso play a role in apoptosis through regulation of the JNK and TGF-beta signaling.Involved in hematopoiesis. Originally identified as a common site of viral integration inmurine myeloid leukemia. Involved in human myeloid disorders through chromosometranslocation and inversion and is also implicated in solid tumor formation. At least sixisoforms of the human protein are formed due to alternative usage of 5'-ends, alternative

splicing, and intergenic splicing which results in the formation of a fusion protein withMDS1, which can be expressed in normal tissues.