General Information of Disease (ID: DIS65TYQ)

Disease Name Lymphoid leukemia
Synonyms
lymphoid leukaemia (disease); lymphogenous leukaemia; lymphogenous leukemia; lymphoid leukemia (disease); lymphoid leukemia; leukemia, LYMPHOCYTIC, malignant; lymphocytic leukaemia; subacute lymphoid leukaemia; lymphocytic leukemia; subacute lymphoid leukemia
Definition
A malignant lymphocytic neoplasm of B-cell or T-cell lineage involving primarily the bone marrow and the peripheral blood. This category includes precursor or acute lymphoblastic leukemias and chronic leukemias.
Disease Hierarchy
DISNAKFL: Leukemia
DIS9S8BC: Lymphoid neoplasm
DIS65TYQ: Lymphoid leukemia
Disease Identifiers
MONDO ID
MONDO_0005402
MESH ID
D007945
UMLS CUI
C0023448
MedGen ID
9728
HPO ID
HP:0005526
SNOMED CT ID
1172709000

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 30 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
AICDA TTKRTP6 Limited Biomarker [1]
BCL6 TTC9YX5 Limited Altered Expression [2]
CASP10 TTX5HEK Limited Biomarker [3]
CD22 TTM6QSK Limited Biomarker [4]
FCER2 TTCH6MU Limited Genetic Variation [5]
IL3RA TTENHJ0 Limited Altered Expression [6]
LCK TT860QF Limited Biomarker [7]
LYN TT1RWNJ Limited Biomarker [8]
NKX3-1 TT1E0JK Limited Altered Expression [9]
PLD2 TTRLMKF Limited Altered Expression [10]
SERPINA6 TTJL8VG Limited Altered Expression [11]
TCF3 TTULOD8 Limited Biomarker [12]
ZAP70 TTUMHT8 Limited Altered Expression [13]
ZFP36L1 TT8QVJO Limited Genetic Variation [14]
ASPA TT6TLZP Disputed Biomarker [15]
CD52 TTQT5S9 Disputed Biomarker [16]
CD58 TT5KSBY Disputed Altered Expression [17]
CSF3R TTC70AJ Disputed Biomarker [18]
FDPS TTIKWV4 Disputed Biomarker [19]
LMO2 TTFX379 Disputed Biomarker [20]
SELPLG TTS5K8U Disputed Biomarker [21]
ABL1 TT6B75U Strong Genetic Variation [22]
ATM TTKBM7V Strong Genetic Variation [23]
CD19 TTW640A Strong Biomarker [24]
CD38 TTPURFN Strong Biomarker [25]
NR1I3 TTRANFM Strong Biomarker [26]
PAX5 TTA4REJ Strong Genetic Variation [27]
PDK3 TTDEQIP Strong Biomarker [28]
TBL1XR1 TTYXT16 Strong Biomarker [29]
TERT TTQY2EJ Strong Biomarker [30]
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⏷ Show the Full List of 30 DTT(s)
This Disease Is Related to 2 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
ABCC11 DTWN7FC Limited Biomarker [31]
SLC25A21 DT2UQYR Strong Biomarker [32]
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This Disease Is Related to 1 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
TPMT DEFQ8VO Limited Biomarker [33]
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This Disease Is Related to 62 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
AFF4 OTTL5Y8R Limited Altered Expression [34]
ASPG OT5E2EKR Limited Biomarker [35]
ATP11A OT7M9ZDK Limited Altered Expression [36]
BAALC OTUZSRVF Limited Altered Expression [37]
BLNK OTSSPF6F Limited Altered Expression [38]
CMPK2 OTOG90R0 Limited Altered Expression [39]
CNTNAP1 OT5Y03EU Limited Biomarker [40]
CTDSPL OTZJ0CZK Limited Posttranslational Modification [41]
DERL1 OTJUS74N Limited Genetic Variation [42]
DNTT OTFSEF12 Limited Altered Expression [43]
ELP2 OTBXG37N Limited Biomarker [44]
FMN2 OTUY7BSV Limited Biomarker [45]
GCSAM OTZNOPYK Limited Altered Expression [12]
GFI1 OT9HB9H8 Limited Altered Expression [46]
GLIS2 OTOUUV1X Limited Biomarker [47]
GML OTHKIB62 Limited Biomarker [48]
HOXC5 OTPQTLKZ Limited Altered Expression [49]
KDM2B OTDMCVW7 Limited Biomarker [50]
LEF1 OTWS5I5H Limited Biomarker [51]
MECOM OTP983W8 Limited Biomarker [52]
MYADM OTZTZI7P Limited Altered Expression [53]
MYOD1 OTV2S79X Limited Posttranslational Modification [54]
NFIL3 OTQH9HM3 Limited Altered Expression [55]
NR2E1 OTW47GKM Limited Genetic Variation [56]
PGP OT6QQ7OR Limited Altered Expression [57]
RAP1GDS1 OTH70UHD Limited Biomarker [58]
RCSD1 OTOICQFW Limited Genetic Variation [59]
RPS14 OTB90KV5 Limited Biomarker [60]
SIX6 OTD1RD9D Limited Biomarker [9]
SMPD3 OTHQBETH Limited Genetic Variation [61]
TAL1 OTX4K6QZ Limited Altered Expression [62]
TFIP11 OT7NVSWU Limited Altered Expression [44]
TLX1 OTVN0MNW Limited Genetic Variation [63]
TLX3 OTBUHHK3 Limited Genetic Variation [63]
TP53BP2 OTOWJ2Y4 Limited Altered Expression [64]
TRIM33 OT0KS4J7 Limited Biomarker [65]
A1CF OTJBKFA1 Disputed Biomarker [15]
DOCK8 OTNQLL21 Disputed Genetic Variation [66]
FBXW11 OT2A6RLR Disputed Altered Expression [67]
GGPS1 OTVEHG28 Disputed Biomarker [19]
NOL3 OT1K0L0D Disputed Biomarker [68]
ROPN1L OTRWZJ68 Disputed Biomarker [15]
IKZF1 OTCW1FKL moderate Biomarker [69]
PBX1 OTORABGO moderate Biomarker [24]
ARR3 OTRZ00CH Strong Biomarker [26]
BCR OTCN76C1 Strong Genetic Variation [22]
CLPTM1L OTDJWQXI Strong Biomarker [30]
CXADR OT9ZP02A Strong Biomarker [26]
ERG OTOTX9VU Strong Biomarker [70]
ETV6 OTCZMG61 Strong Genetic Variation [71]
EVPL OTZIAFEK Strong Posttranslational Modification [40]
IPCEF1 OTOUIHID Strong Biomarker [30]
IRX3 OTLJ48FG Strong Altered Expression [72]
LYL1 OTCNOV1M Strong Genetic Variation [73]
NUP98 OTNT12G2 Strong Biomarker [74]
POT1 OTNBXJCQ Strong Biomarker [30]
SPG7 OT8OY9ST Strong Biomarker [26]
TBC1D9 OTSSCTB5 Strong Genetic Variation [75]
TMEM132D OTV6I4Z0 Strong Biomarker [76]
TRIM13 OTQIUACB Strong Biomarker [26]
GFER OTVK43OK Definitive Altered Expression [77]
SIAH2 OTKED2XN Definitive Biomarker [78]
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⏷ Show the Full List of 62 DOT(s)

References

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5 Guess what: Chronic 13q14.3+/CD5-/CD23+ lymphocytic leukemia in blood and t(11;14)(q13;q32)+/CD5+/CD23- mantle cell lymphoma in lymph nodes!.Cytometry B Clin Cytom. 2003 Jan;51(1):41-4. doi: 10.1002/cyto.b.10005.
6 Distinct expression patterns of CD123 and CD34 on normal bone marrow B-cell precursors ("hematogones") and B lymphoblastic leukemia blasts.Am J Clin Pathol. 2009 Oct;132(4):573-80. doi: 10.1309/AJCPO4DS0GTLSOEI.
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8 Geldanamycin-induced Lyn dissociation from aberrant Hsp90-stabilized cytosolic complex is an early event in apoptotic mechanisms in B-chronic lymphocytic leukemia.Blood. 2008 Dec 1;112(12):4665-74. doi: 10.1182/blood-2008-02-139139. Epub 2008 Sep 2.
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14 Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia.Nat Immunol. 2010 Aug;11(8):717-24. doi: 10.1038/ni.1901. Epub 2010 Jul 11.
15 Interaction between Gallic acid and Asparaginase to potentiate anti-proliferative effect on lymphoblastic leukemia cell line.Biomed Pharmacother. 2017 Dec;96:1045-1054. doi: 10.1016/j.biopha.2017.11.122. Epub 2017 Dec 6.
16 Loss of the GPI-anchor in B-lymphoblastic leukemia by epigenetic downregulation of PIGH expression.Am J Hematol. 2019 Jan;94(1):93-102. doi: 10.1002/ajh.25337. Epub 2018 Nov 25.
17 Role of CD81 and CD58 in minimal residual disease detection in pediatric B lymphoblastic leukemia.Int J Lab Hematol. 2018 Jun;40(3):343-351. doi: 10.1111/ijlh.12795. Epub 2018 Mar 2.
18 Expression and role of granulocyte macrophage colony-stimulating factor receptor (GM-CSFR) and granulocyte colony-stimulating factor receptor (G-CSFR) on Ph-positive acute B lymphoblastic leukemia.Hematology. 2018 Sep;23(8):439-447. doi: 10.1080/10245332.2018.1426540. Epub 2018 Jan 17.
19 Geranylgeranyl diphosphate synthase inhibition induces apoptosis that is dependent upon GGPP depletion, ERK phosphorylation and caspase activation.Cell Death Dis. 2017 Mar 16;8(3):e2678. doi: 10.1038/cddis.2017.101.
20 ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms.Haematologica. 2019 Aug;104(8):1608-1616. doi: 10.3324/haematol.2018.207837. Epub 2019 Jan 24.
21 Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43.Cancers (Basel). 2019 Aug 27;11(9):1253. doi: 10.3390/cancers11091253.
22 A near-haploid clone harboring a BCR/ABL1 gene fusion in an adult patient with newly diagnosed B-lymphoblastic leukemia.Genes Chromosomes Cancer. 2019 Sep;58(9):665-668. doi: 10.1002/gcc.22744. Epub 2019 Mar 18.
23 Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia.Haematologica. 2010 Jan;95(1):158-62. doi: 10.3324/haematol.2009.007526. Epub 2009 Jul 7.
24 Anti-CD19 chimeric antigen receptors T cells for the treatment of relapsed or refractory E2A-PBX1 positive acute lymphoblastic leukemia: report of three cases.Leuk Lymphoma. 2019 Jun;60(6):1454-1461. doi: 10.1080/10428194.2018.1533127. Epub 2019 Feb 4.
25 Expression levels of CD38 in T cells predict course of disease in male patients with B-chronic lymphocytic leukemia.Blood. 2006 Nov 1;108(9):2950-6. doi: 10.1182/blood-2006-03-010553. Epub 2006 Jul 6.
26 Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor Engineered T Cells.Hum Gene Ther. 2019 Apr;30(4):497-510. doi: 10.1089/hum.2018.119. Epub 2019 Jan 23.
27 Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues.Pediatr Blood Cancer. 2017 Jul;64(7). doi: 10.1002/pbc.26363. Epub 2016 Dec 13.
28 The lncRNA-DLEU2/miR-186-5p/PDK3 axis promotes the progress of glioma cells.Am J Transl Res. 2019 Aug 15;11(8):4922-4934. eCollection 2019.
29 Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model.J Biol Chem. 2014 Jul 25;289(30):20502-15. doi: 10.1074/jbc.M114.569889.
30 A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.
31 AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations.Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10398-403. doi: 10.1073/pnas.171321298.
32 Mouse and human ornithine decarboxylase genes. Methylation polymorphism and amplification.Biochem J. 1987 Feb 15;242(1):205-10. doi: 10.1042/bj2420205.
33 Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine.Leukemia. 2001 Nov;15(11):1706-12. doi: 10.1038/sj.leu.2402259.
34 The super elongation complex family of RNA polymerase II elongation factors: gene target specificity and transcriptional output.Mol Cell Biol. 2012 Jul;32(13):2608-17. doi: 10.1128/MCB.00182-12. Epub 2012 Apr 30.
35 Universal premedication and therapeutic drug monitoring for asparaginase-based therapy prevents infusion-associated acute adverse events and drug substitutions.Pediatr Blood Cancer. 2019 Aug;66(8):e27797. doi: 10.1002/pbc.27797. Epub 2019 May 16.
36 Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive lymphoblastic leukemia by increased expression of a novel ABC transporter homolog ATP11a.Blood. 2005 Aug 15;106(4):1355-61. doi: 10.1182/blood-2004-09-3655. Epub 2005 Apr 28.
37 Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome.J Clin Oncol. 2007 Aug 20;25(24):3739-45. doi: 10.1200/JCO.2007.11.5253. Epub 2007 Jul 23.
38 SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells.Oncogene. 2006 Aug 24;25(37):5180-6. doi: 10.1038/sj.onc.1209520. Epub 2006 Apr 24.
39 Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria.J Biol Chem. 2008 Jan 18;283(3):1563-1571. doi: 10.1074/jbc.M707997200. Epub 2007 Nov 13.
40 Pak1 gene functioned differentially in different BCR-ABL subtypes in leukemiagenesis and treatment response through STAT5 pathway.Leuk Res. 2019 Apr;79:6-16. doi: 10.1016/j.leukres.2019.01.012. Epub 2019 Jan 24.
41 Silencing of bidirectional promoters by DNA methylation in tumorigenesis.Cancer Res. 2006 May 15;66(10):5077-84. doi: 10.1158/0008-5472.CAN-05-2629.
42 Secondary chromosomal abnormalities in acute leukemias.Leukemia. 1994 Jun;8(6):953-62.
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44 STIP Regulates ERK1/2 Signaling Pathway Involved in Interaction with PP1 in Lymphoblastic Leukemia.Curr Mol Med. 2016;16(8):767-775. doi: 10.2174/1566524016666161018154401.
45 Gene profiling of Graffi murine leukemia virus-induced lymphoid leukemias: identification of leukemia markers and Fmn2 as a potential oncogene.Blood. 2011 Feb 10;117(6):1899-910. doi: 10.1182/blood-2010-10-311001. Epub 2010 Dec 6.
46 GFI1 facilitates efficient DNA repair by regulating PRMT1 dependent methylation of MRE11 and 53BP1.Nat Commun. 2018 Apr 12;9(1):1418. doi: 10.1038/s41467-018-03817-5.
47 Agranular CD4+CD56+ blastic natural killer leukemia/lymphoma.Ann Hematol. 2001 Apr;80(4):228-31. doi: 10.1007/s002770000257.
48 Philadelphia chromosome positive chronic myelogenous leukemia developing in a patient with acute lymphoblastic leukemia.Cancer. 1979 May;43(5):1782-7. doi: 10.1002/1097-0142(197905)43:5<1782::aid-cncr2820430531>3.0.co;2-j.
49 HOXC4, HOXC5, and HOXC6 expression in primary cutaneous lymphoid lesions. High expression of HOXC5 in anaplastic large-cell lymphomas.Am J Pathol. 1997 Oct;151(4):1067-74.
50 Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis.J Clin Invest. 2016 Mar 1;126(3):905-20. doi: 10.1172/JCI84014. Epub 2016 Jan 25.
51 Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1.Med Mol Morphol. 2013 Mar;46(1):14-9. doi: 10.1007/s00795-012-0002-z. Epub 2013 Jan 17.
52 SUMO1 negatively regulates the transcriptional activity of EVI1 and significantly increases its co-localization with EVI1 after treatment with arsenic trioxide.Biochim Biophys Acta. 2013 Oct;1833(10):2357-68. doi: 10.1016/j.bbamcr.2013.06.003. Epub 2013 Jun 13.
53 Membrane protein hMYADM preferentially expressed in myeloid cells is up-regulated during differentiation of stem cells and myeloid leukemia cells.Life Sci. 2007 Jan 9;80(5):420-9. doi: 10.1016/j.lfs.2006.09.043. Epub 2006 Oct 14.
54 The diagnositc significance of Myf-3 hypermethylation in malignant lymphoproliferative disorders.Leukemia. 2001 Apr;15(4):583-9. doi: 10.1038/sj.leu.2402080.
55 Correlation of glucocorticoid-mediated E4BP4 upregulation with altered expression of pro- and anti-apoptotic genes in CEM human lymphoblastic leukemia cells.Biochem Biophys Res Commun. 2014 Aug 29;451(3):382-8. doi: 10.1016/j.bbrc.2014.07.103. Epub 2014 Aug 4.
56 The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21.Genomics. 1998 May 15;50(1):34-43. doi: 10.1006/geno.1998.5270.
57 In vitro induction of myeloid leukemia-specific CD4 and CD8 T cells by CD40 ligand-activated B cells gene modified to express primary granule proteins.Clin Cancer Res. 2005 Jun 15;11(12):4495-503. doi: 10.1158/1078-0432.CCR-04-2363.
58 The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.Blood. 1999 Sep 15;94(6):2072-9.
59 RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal translocations.Int J Hematol. 2011 Sep;94(3):255-260. doi: 10.1007/s12185-011-0910-z. Epub 2011 Aug 24.
60 Possible new genetic marker for human lymphoid leukemias as detected by ribosomal protein S14 cDNA.Leukemia. 1993 Feb;7(2):318-22.
61 Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias.Blood. 2008 May 1;111(9):4716-22. doi: 10.1182/blood-2007-10-113068. Epub 2008 Feb 25.
62 Enhanced Notch activation is advantageous but not essential for T cell lymphomagenesis in Id1 transgenic mice.PLoS One. 2012;7(2):e32944. doi: 10.1371/journal.pone.0032944. Epub 2012 Feb 29.
63 Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia.Ann Lab Med. 2012 May;32(3):220-4. doi: 10.3343/alm.2012.32.3.220. Epub 2012 Apr 18.
64 Attenuated expression of apoptosis stimulating protein of p53-2 (ASPP2) in human acute leukemia is associated with therapy failure.PLoS One. 2013 Nov 27;8(11):e80193. doi: 10.1371/journal.pone.0080193. eCollection 2013.
65 The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer.Elife. 2015 Apr 28;4:e06377. doi: 10.7554/eLife.06377.
66 Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma.J Clin Immunol. 2019 Aug;39(6):592-595. doi: 10.1007/s10875-019-00663-y. Epub 2019 Jul 2.
67 Fbxw11 promotes the proliferation of lymphocytic leukemia cells through the concomitant activation of NF-B and -catenin/TCF signaling pathways.Cell Death Dis. 2018 Apr 1;9(4):427. doi: 10.1038/s41419-018-0440-1.
68 A QA Program for MRD Testing Demonstrates That Systematic Education Can Reduce Discordance Among Experienced Interpreters.Cytometry B Clin Cytom. 2018 Mar;94(2):239-249. doi: 10.1002/cyto.b.21528. Epub 2017 May 5.
69 Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study.J Clin Oncol. 2018 Sep 10;36(26):2726-2735. doi: 10.1200/JCO.2018.78.3050. Epub 2018 Jul 25.
70 ERG induces a mesenchymal-like state associated with chemoresistance in leukemia cells.Oncotarget. 2014 Jan 30;5(2):351-62. doi: 10.18632/oncotarget.1449.
71 Minimal residual disease monitoring in childhood B lymphoblastic leukemia with t(12;21)(p13;q22); ETV6-RUNX1: concordant results using quantitation of fusion transcript and flow cytometry.Int J Lab Hematol. 2017 Apr;39(2):121-128. doi: 10.1111/ijlh.12593. Epub 2016 Dec 22.
72 Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.Cell Rep. 2018 Jan 16;22(3):638-652. doi: 10.1016/j.celrep.2017.12.063.
73 Shared roles for Scl and Lyl1 in murine platelet production and function.Blood. 2019 Sep 5;134(10):826-835. doi: 10.1182/blood.2019896175. Epub 2019 Jul 12.
74 NUP98/11p15 translocations affect CD34+ cells in myeloid and T lymphoid leukemias.Leuk Res. 2015 Jul;39(7):769-72. doi: 10.1016/j.leukres.2015.04.014. Epub 2015 May 7.
75 Association of MDR1 G2677T polymorphism and leukemia risk: evidence from a meta-analysis.Tumour Biol. 2014 Mar;35(3):2191-7. doi: 10.1007/s13277-013-1291-0. Epub 2013 Oct 20.
76 Long Chain Alkyl Esters of Hydroxycinnamic Acids as Promising Anticancer Agents: Selective Induction of Apoptosis in Cancer Cells.J Agric Food Chem. 2017 Aug 23;65(33):7228-7239. doi: 10.1021/acs.jafc.7b01388. Epub 2017 Aug 8.
77 Decreased expression of the augmenter of liver regeneration results in growth inhibition and increased chemosensitivity of acute T lymphoblastic leukemia cells.Oncol Rep. 2017 Nov;38(5):3130-3136. doi: 10.3892/or.2017.5984. Epub 2017 Sep 21.
78 The expression and function of E3 ligase SIAH2 in acute T lymphoblastic leukemia.Leuk Res. 2016 Mar;42:28-36. doi: 10.1016/j.leukres.2016.01.013. Epub 2016 Jan 28.