{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T18:15:05Z","timestamp":1785608105929,"version":"3.56.0"},"reference-count":123,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,9,1]]},"abstract":"<jats:p> ABSTRACT: Anaplastic large-cell lymphoma (ALCL) provides an excellent example of how molecular insights into tumor pathogenesis are influencing and improving tumor classification. ALCL was described initially as a subtype of T-cell\/null-cell lymphoma characterized by unusual tumor cell morphology and the expression of CD30. However, it was soon recognized that a subset of ALCLs contained chromosomal translocations involving anaplastic lymphoma kinase (ALK), a novel receptor tyrosine kinase gene. These rearrangements create chimeric genes encoding self-associating, constitutively active ALK fusion proteins that activate a number of downstream effectors, including phospholipase C-gamma, phosphoinositol 3'-kinase, RAS, and signal transducer and activator of transcription proteins, all of which seem potentially important in cellular transformation. Not all tumors classified as ALCLs have ALK rearrangements and, conversely, ALK rearrangements occur in lymphomas of widely varying morphology. Hence, only molecular markers can reliably identify ALK<jats:sup>+<\/jats:sup> ALCL. The importance of doing so is reflected by clinical studies suggesting that ALK<jats:sup>+<\/jats:sup> ALCLs have a significantly better prognosis than other aggressive peripheral T-cell or B-cell lymphomas, including ALK<jats:sup>\u2212<\/jats:sup> ALCLs. The unique molecular pathogenesis of ALK<jats:sup>+<\/jats:sup> ALCL is likely to lead to novel therapeutic approaches directed at specific inhibition of ALK or downstream effectors. <\/jats:p>","DOI":"10.1200\/jco.2002.12.033","type":"journal-article","created":{"date-parts":[[2002,8,29]],"date-time":"2002-08-29T19:45:09Z","timestamp":1030650309000},"page":"3691-3702","source":"Crossref","is-referenced-by-count":95,"title":["Molecular Biology of Anaplastic Lymphoma Kinase\u2013Positive Anaplastic Large-Cell Lymphoma"],"prefix":"10.1200","volume":"20","author":[{"given":"Jeffery L.","family":"Kutok","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon C.","family":"Aster","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V66.4.848.848"},{"key":"R2-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198804000-00002"},{"key":"R3-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1989.tb03038.x"},{"key":"R4-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199005000-00003"},{"key":"R5-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1987.tb02687.x"},{"key":"R6-113092","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(89)90134-3"},{"key":"R7-113092","doi-asserted-by":"crossref","unstructured":"Stansfeld  AG,   Diebold  J,   Noel  H,  et al:  Updated Kiel classification for lymphomas.  Lancet 1:  292,1988-293,","DOI":"10.1016\/S0140-6736(88)90367-4"},{"key":"R8-113092","doi-asserted-by":"publisher","DOI":"10.1038\/299065a0"},{"key":"R9-113092","unstructured":"Kadin  M,   Nasu  K,   Sako  D,  et al:  Lymphomatoid papulosis:  A cutaneous proliferation of activated helper T cells expressing Hodgkin\u2019s disease-associated antigens.   Am J Pathol 119:  315,1985-325,"},{"key":"R10-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(18)30870-2"},{"key":"R11-113092","unstructured":"Isaacson  PG:   Gastrointestinal lymphomas of T- and B-cell types.  Mod Pathol 12:  151,1999-158,"},{"key":"R12-113092","unstructured":"Kaudewitz  P,   Stein  H,   Dallenbach  F,  et al:  Primary and secondary cutaneous Ki-1+ (CD30+) anaplastic large cell lymphomas:  Morphologic, immunohistologic, and clinical-characteristics.   Am J Pathol 135:  359,1989-367,"},{"key":"R13-113092","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.44.2.119"},{"key":"R14-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.9.3517.bloodjournal8693517"},{"key":"R15-113092","doi-asserted-by":"crossref","unstructured":"Downing  JR,   Ladanyi  M,   Raffeld  M,  et al:  Large-cell anaplastic lymphoma-specific translocation in Hodgkin\u2019s disease.  Lancet 345:  918,1995-921,","DOI":"10.1016\/S0140-6736(95)90030-6"},{"key":"R16-113092","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008241904019"},{"key":"R17-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.4.1394"},{"key":"R18-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.5.1765.1765"},{"key":"R19-113092","unstructured":"Ladanyi  M,   Cavalchire  G,   Morris  SW,  et al:  Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin\u2019s disease.  Am J Pathol 145:  1296,1994-1300,"},{"key":"R20-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199712000-00004"},{"key":"R21-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.10.2845.bloodjournal85102845"},{"key":"R22-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.6.2321.bloodjournal8662321"},{"key":"R23-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1988.tb02021.x"},{"key":"R24-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.5.1694.bloodjournal8651694"},{"key":"R25-113092","doi-asserted-by":"publisher","DOI":"10.3109\/10428190109097716"},{"key":"R26-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1997.tb01090.x"},{"key":"R27-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.8.3437.bloodjournal8783437"},{"key":"R28-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1997.tb01101.x"},{"key":"R29-113092","unstructured":"Pittaluga  S,   Wiodarska  I,   Pulford  K,  et al:  The monoclonal antibody ALK1 identifies a distinct morphological subtype of anaplastic large cell lymphoma associated with 2p23\/ALK rearrangements.  Am J Pathol 151:  343,1997-351,"},{"key":"R30-113092","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008278100116"},{"key":"R31-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.8.2467.2467"},{"key":"R32-113092","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.5.895"},{"key":"R33-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.5.1954.bloodjournal8651954"},{"key":"R34-113092","unstructured":"Falini  B,   Pileri  S,   Zinzani  PL,  et al:  ALK+ lymphoma:  Clinico-pathological findings and outcome.   Blood 93:  2697,1999-2706,"},{"key":"R35-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.11.3913"},{"key":"R36-113092","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.3.955"},{"key":"R37-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199911000-00009"},{"key":"R38-113092","unstructured":"Le Beau MM,    Bitter  MA,   Larson  RA,  et al:  The t(2;5)(p23;q35):  A recurring chromosomal abnormality in Ki-1- positive anaplastic large cell lymphoma.   Leukemia 3:  866,1989-870,"},{"key":"R39-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.3.806.806"},{"key":"R40-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1989.tb06270.x"},{"key":"R41-113092","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1990.tb02560.x"},{"key":"R42-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199004000-00001"},{"key":"R43-113092","doi-asserted-by":"publisher","DOI":"10.1126\/science.8122112"},{"key":"R44-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204594"},{"key":"R45-113092","doi-asserted-by":"publisher","DOI":"10.1016\/0959-437X(94)90086-8"},{"key":"R46-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1200849"},{"key":"R47-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201062"},{"key":"R48-113092","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02574.x"},{"key":"R49-113092","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.6.1225"},{"key":"R50-113092","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90241-9"},{"key":"R51-113092","doi-asserted-by":"publisher","DOI":"10.1021\/bi00429a017"},{"key":"R52-113092","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(95)00044-H"},{"key":"R53-113092","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.5.1629"},{"key":"R54-113092","doi-asserted-by":"crossref","unstructured":"Feuerstein  N,   Chan  PK,   Mond  JJ:   Identification of numatrin, the nuclear matrix protein associated with induction of mitogenesis, as the nucleolar protein B23:  Implication for the role of the nucleolus in early transduction of mitogenic signals.   J Biol Chem 263:  10608,1988-10612,","DOI":"10.1016\/S0021-9258(18)38014-1"},{"key":"R55-113092","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910460328"},{"key":"R56-113092","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90093-T"},{"key":"R57-113092","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(91)90367-4"},{"key":"R58-113092","unstructured":"Derenzini  M,   Sirri  V,   Trere  D,  et al:  The quantity of nucleolar proteins nucleolin and protein B23 is related to cell doubling time in human cancer cells.  Lab Invest 73:  497,1995-502,"},{"key":"R59-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(96)80014-0"},{"key":"R60-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.12.4668"},{"key":"R61-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.2.632"},{"key":"R62-113092","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.4.2312"},{"key":"R63-113092","unstructured":"Shiota  M,   Fujimoto  J,   Semba  T,  et al:  Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3.  Oncogene 9:  1567,1994-1574,"},{"key":"R64-113092","doi-asserted-by":"publisher","DOI":"10.1007\/BF03349721"},{"key":"R65-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.9.3088"},{"key":"R66-113092","doi-asserted-by":"crossref","unstructured":"Hernandez  L,   Pinyol  M,   Hernandez  S,  et al:  TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.  Blood 94:  3265,1999-3268,","DOI":"10.1182\/blood.V94.9.3265"},{"key":"R67-113092","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.11.6118"},{"key":"R68-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201596"},{"key":"R69-113092","unstructured":"Trinei  M,   Lanfrancone  L,   Campo  E,  et al:  A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma.  Cancer Res 60:  793,2000-798,"},{"key":"R70-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64945-0"},{"key":"R71-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.10.3204"},{"key":"R72-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61711-7"},{"key":"R73-113092","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780249"},{"key":"R74-113092","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.6.8.1061"},{"key":"R75-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(98)00103-4"},{"key":"R76-113092","unstructured":"Mason  DY,   Pulford  KA,   Bischof  D,  et al:  Nucleolar localization of the nucleophosmin-anaplastic lymphoma kinase is not required for malignant transformation.  Cancer Res 58:  1057,1998-1062,"},{"key":"R77-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.8.2683"},{"key":"R78-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400661"},{"key":"R79-113092","unstructured":"Yoneda-Kato  N,   Look  AT,   Kirstein  MN,  et al:  The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1.  Oncogene 12:  265,1996-275,"},{"key":"R80-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65098-5"},{"key":"R81-113092","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4181"},{"key":"R82-113092","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.6951"},{"key":"R83-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.8.2901"},{"key":"R84-113092","unstructured":"Griffin  CA,   Hawkins  AL,   Dvorak  C,  et al:  Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.  Cancer Res 59:  2776,1999-2780,"},{"key":"R85-113092","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880352"},{"key":"R86-113092","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.23523"},{"key":"R87-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64550-6"},{"key":"R88-113092","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.01097.x"},{"key":"R89-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64690-1"},{"key":"R90-113092","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199603)15:3<173::AID-GCC5>3.0.CO;2-#"},{"key":"R91-113092","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9461"},{"key":"R92-113092","unstructured":"Nieborowska-Skorska  M,   Slupianek  A,   Xue  L,  et al:  Role of signal transducer and activator of transcription 5 in nucleophosmin\/anaplastic lymphoma kinase-mediated malignant transformation of lymphoid cells.  Cancer Res 61:  6517,2001-6523,"},{"key":"R93-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00067-8"},{"key":"R94-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3390"},{"key":"R95-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.13.4319"},{"key":"R96-113092","unstructured":"Slupianek  A,   Nieborowska-Skorska  M,   Hoser  G,  et al:  Role of phosphatidylinositol 3-kinase-Akt pathway in nucleophosmin\/anaplastic lymphoma kinase-mediated lymphomagenesis.  Cancer Res 61:  2194,2001-2199,"},{"key":"R97-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204870"},{"key":"R98-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(99)00116-2"},{"key":"R99-113092","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204128"},{"key":"R100-113092","unstructured":"Delsol  G,   Al Saati  T,   Gatter  KC,  et al:  Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas:  Diagnostic value in so-called malignant histiocytosis.   Am J Pathol 130:  59,1988-70,"},{"key":"R101-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.6.2076"},{"key":"R102-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.10.4005.bloodjournal88104005"},{"key":"R103-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.3.980"},{"key":"R104-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199309000-00001"},{"key":"R105-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65629-5"},{"key":"R106-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200011000-00010"},{"key":"R107-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200009000-00018"},{"key":"R108-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200107000-00009"},{"key":"R109-113092","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880289"},{"key":"R110-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.11.3648.bloodjournal84113648"},{"key":"R111-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.1.284.284"},{"key":"R112-113092","unstructured":"Pileri  SA,   Pulford  K,   Mori  S,  et al:  Frequent expression of the NPM-ALK chimeric fusion protein in anaplastic large-cell lymphoma, lympho-histiocytic type.  Am J Pathol 150:  1207,1997-1211,"},{"key":"R113-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.5.1483"},{"key":"R114-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65042-0"},{"key":"R115-113092","doi-asserted-by":"publisher","DOI":"10.1097\/00019606-199609000-00002"},{"key":"R116-113092","unstructured":"Brugieres  L,   Deley  MC,   Pacquement  H,  et al:  CD30(+) anaplastic large-cell lymphoma in children:  Analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology.   Blood 92:  3591,1998-3598,"},{"key":"R117-113092","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3653"},{"key":"R119-113092","unstructured":"Falini  B,   Pulford  K,   Pucciarini  A,  et al:  Lymphomas expressing ALK fusion protein(s) other than NPM-ALK.  Blood 94:  3509,1999-3515,"},{"key":"R120-113092","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441402"},{"key":"R121-113092","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441401"},{"key":"R122-113092","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441404"},{"key":"R123-113092","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9083"},{"key":"R124-113092","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(01)00688-9"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2002.12.033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:54:00Z","timestamp":1653515640000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2002.12.033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,9,1]]},"references-count":123,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2002,9,1]]}},"alternative-id":["10.1200\/JCO.2002.12.033"],"URL":"https:\/\/doi.org\/10.1200\/jco.2002.12.033","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,9,1]]}}}