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RGD DISEASE ONTOLOGY - ANNOTATIONS

RGD uses the Human Disease Ontology (DO, https://disease-ontology.org/) for disease curation across species. RGD automatically downloads each new release of the ontology on a monthly basis. Some additional terms which are required for RGD's curation purposes but are not currently covered in the official version of DO have been added. As corresponding terms are added to DO, these custom terms are retired and the DO terms substituted in existing annotations and subsequently used for curation.

Term:B-Cell Chronic Lymphocytic Leukemia
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Accession:DOID:9002227 term browser browse the term
Definition:A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
Synonyms:exact_synonym: BCLL;   CLL Lymphoplasmacytoid Lymphoma;   CLL Lymphoplasmacytoid Lymphomas;   Chronic B-Lymphocytic Leukemia;   Chronic Lymphoblastic Leukemia;   Chronic Lymphoblastic Leukemias;   DBM;   Diffuse Well Differentiated Lymphocytic Lymphoma;   Disrupted In B-Cell Malignancy;   Lymphocytic Lymphoma;   Lymphocytic Lymphomas;   Lymphoma, Small Lymphocytic, Plasmacytoid;   Small Cell Lymphoma;   Small-Cell Lymphomas;   chronic B-cell leukemia;   chronic B-cell leukemias;   chronic B-lymphocytic leukemias;   low-grade B-cell malignancy;   small lymphocytic lymphoma;   small lymphocytic lymphomas;   well-differentiated lymphocytic lymphoma;   well-differentiated lymphocytic lymphomas
 related_synonym: CLLS1;   CLLS2;   CLLS3;   CLLS4;   CLLS5;   chronic lymphocytic leukemia, susceptibility to, 1;   chronic lymphocytic leukemia, susceptibility to, 2;   chronic lymphocytic leukemia, susceptibility to, 3;   chronic lymphocytic leukemia, susceptibility to, 4;   chronic lymphocytic leukemia, susceptibility to, 5
 primary_id: MESH:D015451
 alt_id: MIM:109543;   MIM:151400;   MIM:609630;   MIM:612557;   MIM:612558;   MIM:612559
 xref: NCI:C7540



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B-Cell Chronic Lymphocytic Leukemia term browser
Symbol Object Name Qualifiers Evidence Notes Source PubMed Reference(s) RGD Reference(s) Position
G ABCG2 ATP binding cassette subfamily G member 2 susceptibility ISO DNA:SNPs,haplotype: :rs1481012,rs2231142(human) RGD PMID:21918980 RGD:11080977 NCBI chr32:11,443,778...11,517,674
Ensembl chr32:11,443,780...11,517,674
JBrowse link
G ACOXL acyl-CoA oxidase like ISO CTD Direct Evidence: marker/mechanism CTD PMID:23770605 NCBI chr17:35,269,824...35,617,068
Ensembl chr17:35,269,501...35,617,335
JBrowse link
G AICDA activation induced cytidine deaminase disease_progression ISO RGD PMID:21133730 RGD:11039455 NCBI chr27:37,064,107...37,073,791
Ensembl chr27:37,064,080...37,073,789
JBrowse link
G APOE apolipoprotein E disease_progression ISO RGD PMID:18784741 RGD:11040549 NCBI chr 1:110,525,717...110,528,534
Ensembl chr 1:110,525,722...110,528,440
JBrowse link
G ATM ATM serine/threonine kinase ISO CTD Direct Evidence: marker/mechanism CTD PMID:17968022 NCBI chr 5:24,180,129...24,297,207
Ensembl chr 5:24,182,135...24,297,207
JBrowse link
G BCL11A BCL11 transcription factor A ISO DNA:translocation:5' utr: (human) RGD PMID:11719382 RGD:11100004 NCBI chr10:60,589,298...60,691,997
Ensembl chr10:60,589,708...60,689,073
JBrowse link
G BCL2 BCL2 apoptosis regulator severity
treatment
no_association
ISO protein:increased expression:B cell (human)
DNA:snp:promoter:g.-938C>A (human)
CTD Direct Evidence: marker/mechanism
RGD
CTD
PMID:16960146 PMID:17296974 PMID:17959858 PMID:20001236 PMID:21750559 More... RGD:11522735 RGD:11526104 RGD:11526105 RGD:11526110 NCBI chr 1:13,733,849...13,900,653
Ensembl chr 1:13,731,406...13,900,658
JBrowse link
G BMF Bcl2 modifying factor ISO CTD Direct Evidence: marker/mechanism CTD PMID:23770605 NCBI chr30:7,301,000...7,321,949
Ensembl chr30:7,274,174...7,322,034
JBrowse link
G BRAF B-Raf proto-oncogene, serine/threonine kinase ISO ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia | ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:12068308 PMID:12198537 PMID:12692057 PMID:12960123 PMID:14612909 More... NCBI chr16:8,222,909...8,318,179
Ensembl chr16:8,222,907...8,317,906
JBrowse link
G BTK Bruton tyrosine kinase treatment ISO ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia RGD
ClinVar
PMID:23045577 PMID:24869598 PMID:25741868 PMID:28492532 RGD:11040699 NCBI chr  X:75,270,952...75,302,663
Ensembl chr  X:75,270,979...75,302,562
JBrowse link
G CBL Cbl proto-oncogene severity ISO mRNA,protein:increased expression:CD5+ B cell:
DNA:hypophosphorylation:CD5+ B cell:
RGD PMID:17804547 RGD:11038803 NCBI chr 5:14,600,409...14,676,974
Ensembl chr 5:14,607,013...14,676,956
JBrowse link
G CCDC50 coiled-coil domain containing 50 ISO RGD PMID:19641524 RGD:9685139 NCBI chr34:23,168,594...23,243,221
Ensembl chr34:23,168,525...23,258,497
JBrowse link
G CD40 CD40 molecule ISO RGD PMID:20616215 RGD:5490532 NCBI chr24:33,352,992...33,383,488
Ensembl chr24:33,372,930...33,383,301
JBrowse link
G CD40LG CD40 ligand ISO mouse-human chimeric gene in human RGD PMID:20882050 RGD:11352235 NCBI chr  X:107,001,421...107,023,007
Ensembl chr  X:107,010,890...107,023,006
JBrowse link
G CD5 CD5 molecule ISO CTD Direct Evidence: marker/mechanism CTD PMID:18006695 NCBI chr18:55,216,415...55,235,567
Ensembl chr18:55,217,276...55,235,405
JBrowse link
G CD79B CD79b molecule ISO protein:decreased expression:B lymphocyte, cell surface (human)
DNA:polymorphism:multiple (human)
mRNA, protein:splice variants, alternative forms:exon 3 (human)
RGD PMID:9269755 PMID:10090943 PMID:10552962 RGD:11250403 RGD:151665190 RGD:151665202 NCBI chr 9:11,834,230...11,844,946
Ensembl chr 9:11,842,190...11,844,843
JBrowse link
G CD86 CD86 molecule severity ISO protein:increased expression:peripheral blood mononuclear cell (human) RGD PMID:25179679 RGD:11354969 NCBI chr33:25,256,267...25,318,855
Ensembl chr33:25,256,267...25,318,087
JBrowse link
G CPEB1 cytoplasmic polyadenylation element binding protein 1 ISO CTD Direct Evidence: marker/mechanism CTD PMID:20062064 NCBI chr 3:54,405,140...54,499,614
Ensembl chr 3:54,405,717...54,500,221
JBrowse link
G CTLA4 cytotoxic T-lymphocyte associated protein 4 ISO protein:increased expression:T cell RGD PMID:15914560 PMID:16094420 RGD:11344923 RGD:11352246 NCBI chr37:12,647,712...12,653,874
Ensembl chr37:12,634,563...12,653,874
JBrowse link
G DKC1 dyskerin pseudouridine synthase 1 ISO RGD PMID:18077792 RGD:11251735 NCBI chr  X:122,838,787...122,850,870
Ensembl chr  X:122,838,645...122,850,884
JBrowse link
G DNMT3B DNA methyltransferase 3 beta ISO mRNA:decreased expression: B cell RGD PMID:15467427 RGD:9589146 NCBI chr24:22,096,386...22,123,378
Ensembl chr24:22,096,349...22,122,900
JBrowse link
G ERCC2 ERCC excision repair 2, TFIIH core complex helicase subunit severity ISO DNA:SNP: :p.K751Q (rs13181) (human) RGD PMID:19484764 PMID:22739018 RGD:11252203 RGD:11252204 NCBI chr 1:110,173,781...110,191,612
Ensembl chr 1:110,173,715...110,190,125
JBrowse link
G FARP2 FERM, ARH/RhoGEF and pleckstrin domain protein 2 ISO CTD Direct Evidence: marker/mechanism CTD PMID:20062064 NCBI chr25:51,331,876...51,425,754
Ensembl chr25:51,332,409...51,425,449
JBrowse link
G FAS Fas cell surface death receptor disease_progression ISO RGD PMID:12901972 RGD:11049461 NCBI chr26:38,738,811...38,763,298
Ensembl chr26:38,737,611...38,763,321
JBrowse link
G FBXW7 F-box and WD repeat domain containing 7 ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:25741868 PMID:26619011 NCBI chr15:50,187,579...50,417,188
Ensembl chr15:50,189,240...50,417,195
JBrowse link
G GNAS GNAS complex locus disease_progression ISO DNA:polymorphism:393T>C (human) RGD PMID:17020971 RGD:1601379 NCBI chr24:43,643,409...43,658,641
Ensembl chr24:43,643,405...43,658,657
JBrowse link
G HRAS HRas proto-oncogene, GTPase ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:12835555 PMID:16329078 PMID:16372351 PMID:16835863 PMID:17211612 More... NCBI chr18:25,642,844...25,644,717
Ensembl chr18:25,642,844...25,644,717
JBrowse link
G ICAM1 intercellular adhesion molecule 1 severity ISO RGD PMID:7658704 RGD:11354983 NCBI chr20:50,818,715...50,827,914
Ensembl chr20:50,818,715...50,827,914
JBrowse link
G IFNG interferon gamma susceptibility ISO DNA:polymorphism: :847A>T(human) RGD PMID:19757192 RGD:10755703 NCBI chr10:10,406,866...10,411,698
Ensembl chr10:10,406,867...10,411,698
JBrowse link
G IL10 interleukin 10 disease_progression
no_association
ISO protein:increased expression:serum
DNA:SNPs: :multiple
DNA:SNPs: :rs1800890, rs4072227, rs17015865 (human)
RGD PMID:10638947 PMID:19573080 PMID:22945689 RGD:11041895 RGD:11049165 RGD:11049174 NCBI chr 7:5,933,285...5,937,057
Ensembl chr 7:5,933,285...5,937,057
JBrowse link
G IL19 interleukin 19 ISO CTD Direct Evidence: marker/mechanism CTD PMID:18006695 NCBI chr 7:6,000,994...6,006,959
Ensembl chr 7:6,000,907...6,006,870
JBrowse link
G IL1A interleukin 1 alpha ISO RGD PMID:19074885 RGD:11051968 NCBI chr17:36,969,581...36,979,445
Ensembl chr17:36,970,573...36,979,435
JBrowse link
G IL1B interleukin 1 beta severity ISO DNA:SNP:promoter:-511C>T (human)
protein:decreased expression:plasma:
RGD PMID:10870116 PMID:18271063 RGD:11051967 RGD:11522755 NCBI chr17:37,019,329...37,033,388
Ensembl chr17:37,019,329...37,024,458
JBrowse link
G IL1RN interleukin 1 receptor antagonist ISO protein:decreased expression:plasma: RGD PMID:10870116 RGD:11522755 NCBI chr17:37,236,690...37,250,424
Ensembl chr17:37,212,751...37,249,329
JBrowse link
G IL6 interleukin 6 ISO CTD Direct Evidence: marker/mechanism
protein:increased expression:plasma:
CTD
RGD
PMID:10870116 PMID:18006695 RGD:11522755 NCBI chr14:36,474,268...36,478,519
Ensembl chr14:36,473,394...36,478,519
JBrowse link
G IRF4 interferon regulatory factor 4 disease_progression ISO CTD Direct Evidence: marker/mechanism CTD
RGD
PMID:12079517 PMID:12393648 PMID:18758461 RGD:11526160 RGD:11530024 NCBI chr35:760,367...782,314
Ensembl chr35:767,011...781,339
JBrowse link
G ITGA4 integrin subunit alpha 4 ISO CTD Direct Evidence: marker/mechanism CTD PMID:21093051 NCBI chr36:24,670,464...24,686,719
Ensembl chr36:24,653,408...24,729,057
JBrowse link
G KRAS KRAS proto-oncogene, GTPase ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:2278970 PMID:3122217 PMID:12460918 PMID:15696205 PMID:16361624 More... NCBI chr27:22,261,753...22,296,704
Ensembl chr27:22,257,941...22,293,369
JBrowse link
G LEF1 lymphoid enhancer binding factor 1 ISO CTD Direct Evidence: marker/mechanism CTD PMID:23770605 NCBI chr32:28,516,002...28,633,759
Ensembl chr32:28,517,108...28,634,019
JBrowse link
G LOC100683403 NKG2-A/NKG2-B type II integral membrane protein-like ISO CTD Direct Evidence: marker/mechanism CTD PMID:18006695 NCBI chr27:35,307,892...35,374,397 JBrowse link
G LOC478984 low affinity immunoglobulin gamma Fc region receptor III no_association ISO DNA:SNP:exon:p.F158V (rs396991) (human) RGD PMID:14563637 RGD:11352260 NCBI chr38:21,054,870...21,060,948 JBrowse link
G LRRC56 leucine rich repeat containing 56 ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:12835555 PMID:16329078 PMID:16372351 PMID:16835863 PMID:17211612 More... NCBI chr18:25,647,024...25,662,646
Ensembl chr18:25,647,882...25,664,220
JBrowse link
G MIR143 microRNA mir-143 ISO CTD Direct Evidence: marker/mechanism CTD PMID:17892514 NCBI chr 4:59,534,535...59,534,589
Ensembl chr 4:59,534,535...59,534,594
JBrowse link
G MIR145 microRNA mir-145 ISO CTD Direct Evidence: marker/mechanism CTD PMID:17892514 NCBI chr 4:59,533,128...59,533,210
Ensembl chr 4:59,533,128...59,533,210
JBrowse link
G MS4A1 membrane spanning 4-domains A1 ISO RGD PMID:19911856 RGD:2316994 NCBI chr21:50,722,142...50,734,934
Ensembl chr21:50,722,041...50,733,704
JBrowse link
G MTHFR methylenetetrahydrofolate reductase ISO CTD Direct Evidence: marker/mechanism CTD PMID:16706930 NCBI chr 2:84,445,526...84,457,435
Ensembl chr 2:84,380,919...84,536,818
JBrowse link
G MYD88 MYD88 innate immune signal transduction adaptor ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:21179087 PMID:22931316 PMID:23215570 PMID:23355535 PMID:26619011 More... NCBI chr23:7,901,578...7,905,274
Ensembl chr23:7,901,250...7,904,534
JBrowse link
G NRAS NRAS proto-oncogene, GTPase ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:1654209 PMID:2278970 PMID:2674680 PMID:3122217 PMID:6587382 More... NCBI chr17:52,411,733...52,418,788
Ensembl chr17:52,411,733...52,418,788
JBrowse link
G P2RX7 purinergic receptor P2X 7 ISO CTD Direct Evidence: marker/mechanism CTD PMID:11003599 NCBI chr26:7,928,863...7,983,956
Ensembl chr26:7,940,985...7,983,740
JBrowse link
G PECAM1 platelet and endothelial cell adhesion molecule 1 severity ISO protein:increased expression:B cell (human) RGD PMID:12673718 RGD:11541127 NCBI chr 9:12,166,124...12,219,553
Ensembl chr 9:12,166,775...12,219,778
JBrowse link
G PLCG2 phospholipase C gamma 2 ISO ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia ClinVar PMID:24869598 PMID:28492532 NCBI chr 5:70,054,683...70,233,459
Ensembl chr 5:70,059,255...70,207,049
JBrowse link
G PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1 ISO CTD Direct Evidence: marker/mechanism CTD PMID:23770605 NCBI chr 1:16,469,793...16,472,910
Ensembl chr 1:16,469,793...16,472,910
JBrowse link
G POLB DNA polymerase beta ISO CTD Direct Evidence: marker/mechanism CTD PMID:18006695 NCBI chr16:23,306,359...23,335,352
Ensembl chr16:23,306,367...23,335,322
JBrowse link
G PPP2R5C protein phosphatase 2 regulatory subunit B'gamma ISO CTD Direct Evidence: marker/mechanism CTD PMID:16038780 NCBI chr 8:69,846,311...69,969,409
Ensembl chr 8:69,846,446...69,967,578
JBrowse link
G PRAME PRAME nuclear receptor transcriptional regulator ISO protein:increased expression:mononuclear cell (human) RGD PMID:16620968 RGD:11535021 NCBI chr26:27,124,901...27,137,772
Ensembl chr26:27,124,902...27,136,112
JBrowse link
G PRKD2 protein kinase D2 ISO CTD Direct Evidence: marker/mechanism CTD PMID:18758461 NCBI chr 1:109,206,400...109,241,529
Ensembl chr 1:109,207,067...109,330,007
JBrowse link
G PTGS2 prostaglandin-endoperoxide synthase 2 ISO CTD Direct Evidence: marker/mechanism CTD PMID:16314473 NCBI chr 7:19,668,079...19,674,903
Ensembl chr 7:19,668,082...19,674,903
JBrowse link
G PTPN11 protein tyrosine phosphatase non-receptor type 11 ISO ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia | ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:12161469 PMID:12717436 PMID:14644997 PMID:14982869 PMID:15385933 More... NCBI chr26:9,989,218...10,072,245
Ensembl chr26:9,989,425...10,067,481
JBrowse link
G QPCT glutaminyl-peptide cyclotransferase ISO CTD Direct Evidence: marker/mechanism CTD PMID:23770605 NCBI chr17:29,700,422...29,741,652
Ensembl chr17:29,716,378...29,741,221
JBrowse link
G RBL2 RB transcriptional corepressor like 2 ISO CTD Direct Evidence: marker/mechanism CTD PMID:16038780 NCBI chr 2:62,263,974...62,315,371
Ensembl chr 2:62,265,293...62,315,425
JBrowse link
G SF3B1 splicing factor 3b subunit 1 ISO ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia | ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:23634996 PMID:25741868 PMID:26619011 NCBI chr37:6,922,150...6,962,474
Ensembl chr37:6,924,047...6,962,896
JBrowse link
G SF3B2 splicing factor 3b subunit 2 ISO ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia | ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:26619011 NCBI chr18:51,197,924...51,212,397
Ensembl chr18:51,197,939...51,212,354
JBrowse link
G SP140 SP140 nuclear body protein ISO CTD Direct Evidence: marker/mechanism CTD PMID:18758461 NCBI chr25:42,459,013...42,527,141
Ensembl chr25:42,459,084...42,527,093
JBrowse link
G TERT telomerase reverse transcriptase disease_progression ISO RGD PMID:17344921 RGD:11038662 NCBI chr34:11,288,622...11,307,790
Ensembl chr34:11,288,622...11,307,951
JBrowse link
G TFRC transferrin receptor ISO CTD Direct Evidence: marker/mechanism CTD PMID:16904380 NCBI chr33:29,206,024...29,237,221
Ensembl chr33:29,208,609...29,238,242
JBrowse link
G THBD thrombomodulin ISO RGD PMID:21812019 RGD:5685033 NCBI chr24:599,773...601,649
Ensembl chr24:599,773...601,649
JBrowse link
G TNF tumor necrosis factor disease_progression ISO protein:increased expression:bone marrow, blood, lymphocyte RGD PMID:12010662 PMID:22945689 RGD:10449463 RGD:11041895 NCBI chr12:1,074,561...1,076,425
Ensembl chr12:1,074,552...1,076,425
JBrowse link
G TNFRSF11A TNF receptor superfamily member 11a ISO CTD Direct Evidence: marker/mechanism CTD PMID:16270354 NCBI chr 1:14,504,595...14,555,956
Ensembl chr 1:14,503,033...14,556,041
JBrowse link
G TNFSF11 TNF superfamily member 11 ISO CTD Direct Evidence: marker/mechanism CTD PMID:16270354 NCBI chr22:8,226,931...8,257,926
Ensembl chr22:8,227,555...8,258,645
JBrowse link
G TNFSF13 TNF superfamily member 13 ISO protein:increased expression:serum RGD PMID:15488762 RGD:1549466 NCBI chr 5:32,482,723...32,484,790
Ensembl chr 5:32,482,723...32,484,789
JBrowse link
G TNFSF8 TNF superfamily member 8 ISO CTD Direct Evidence: marker/mechanism CTD PMID:9058727 NCBI chr11:68,979,498...69,006,898
Ensembl chr11:68,982,360...69,007,355
JBrowse link
G TOPBP1 DNA topoisomerase II binding protein 1 ISO CTD Direct Evidence: marker/mechanism CTD PMID:18006695 NCBI chr23:30,517,172...30,578,664
Ensembl chr23:30,516,125...30,578,108
JBrowse link
G TP53 tumor protein p53 disease_progression ISO DNA:deletion: :
ClinVar Annotator: match by term: B-cell chronic lymphocytic leukemia | ClinVar Annotator: match by term: Leukemia, B-cell, chronic
RGD
ClinVar
PMID:253702 PMID:1565143 PMID:1565144 PMID:1631137 PMID:1679237 More... RGD:11075074 NCBI chr 5:32,561,406...32,565,149
Ensembl chr 5:32,560,598...32,574,109
JBrowse link
G VDR vitamin D receptor ISO CTD Direct Evidence: marker/mechanism CTD PMID:12446453 NCBI chr27:6,852,915...6,909,466
Ensembl chr27:6,852,723...6,909,470
JBrowse link
G XPO1 exportin 1 ISO ClinVar Annotator: match by term: Leukemia, B-cell, chronic ClinVar PMID:26619011 NCBI chr10:61,541,647...61,588,397
Ensembl chr10:61,542,211...61,585,054
JBrowse link
G XRCC1 X-ray repair cross complementing 1 no_association
severity
ISO DNA:SNP: :p.R194W (rs1799782), p.R280H (25489) (human)
DNA:SNP: :p.R399Q (rs25487) (human)
RGD PMID:19484764 RGD:11252204 NCBI chr 1:111,548,719...111,571,816
Ensembl chr 1:111,548,719...111,571,816
JBrowse link

Term paths to the root
Path 1
Term Annotations click to browse term
  disease 15720
    disease of cellular proliferation 7512
      Neoplasms by Histologic Type 5208
        lymphoma 538
          chronic lymphocytic leukemia 90
            B-Cell Chronic Lymphocytic Leukemia 76
Path 2
Term Annotations click to browse term
  disease 15720
    disease of anatomical entity 15366
      Immune & Inflammatory Diseases 5198
        immune system disease 4504
          immune system cancer 626
            lymphatic system cancer 626
              lymphoma 538
                lymphoid leukemia 281
                  acute leukemia 270
                    acute lymphoblastic leukemia 268
                      B-cell acute lymphoblastic leukemia 121
                        B-lymphoblastic leukemia/lymphoma 119
                          B-Cell Chronic Lymphocytic Leukemia 76
paths to the root