| Entity | Anaplasic large cell lymphoma (ALCL) with t(2;5)(p23;q35) --> NPM1-ALK |
| Disease | ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); 80% of ALK+ ALCL cases bear a t(2;5) |
| Prognosis | nonetheless, a 80% five yr survival may be associated with this anomaly |
| Cytogenetics | additional anomalies are most often found |
| Hybrid/Mutated Gene | 5' NPM1-3' ALK on der(5) |
| Abnormal Protein | 680 amino acids, 80 kDa; N-term 116 amino acids from NPM1 fused to the 563 C-term aminoacids of ALK (i.e. composed of the oligomerization domain and the metal binding site of NPM1 ,and the entire cytoplasmic portion of ALK); no apparent expression of the ALK/NPM1 counterpart; Characteristic localisation both in the cytoplasm and in the nucleus, due to heterooligomerization of NPM-ALK and normal NPM whereas the normal NPM protein is confined to the nucleus; constitutive activation of the catalytic domain of ALK. |
| Oncogenesis | via the kinase function activated by oligomerization of NPM1-ALK mediated by the NPM1 part |
| | |
| Entity | t(3;5)(q25;q34)/in myeloid malignancies --> NPM - MLF1 |
| Disease | Acute non lymphocytic leukemia (ANLL), myelodysplasia (MDS), chronic myelogenous leukemia in blast crisis (BC-CML); trilineage involvement |
| Prognosis | very poor |
| Cytogenetics | location of breakpoints difficult to ascertain |
| Hybrid/Mutated Gene | 5' NPM-3' MLF1 on der(5) |
| Abnormal Protein | with the 175 N term amino acids of NPM1; nuclear protein |
| | |
| Entity | t(5;17)(q34;q21)/M3-ANLL --> NPM1-RARa |
| Disease | promyelocytic ANLL (M3-ANLL) |
| Cytogenetics | variant translocation of the well known t(15;17) |
| Hybrid/Mutated Gene | 5' NPM1-3' RARa on der(5) |
| Abnormal Protein | with the 117 N term amino acids of NPM1 |
| | |
| Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. |
| Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT |
| Science (New York, N.Y.). 1994 ; 263 (5151) : 1281-1284. |
| PMID 8122112 |
| |
| The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. |
| Yoneda-Kato N, Look AT, Kirstein MN, Valentine MB, Raimondi SC, Cohen KJ, Carroll AJ, Morris SW |
| Oncogene. 1996 ; 12 (2) : 265-275. |
| PMID 8570204 |
| |
| The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. |
| Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ |
| Blood. 1996 ; 87 (3) : 882-886. |
| PMID 8562957 |
| |
| The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. |
| Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ |
| Blood. 1996 ; 87 (3) : 882-886. |
| PMID 8562957 |
| |
| Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region. |
| Chan PK, Chan FY, Morris SW, Xie Z |
| Nucleic acids research. 1997 ; 25 (6) : 1225-1232. |
| PMID 9092633 |
| |
| Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis. |
| Bischof D, Pulford K, Mason DY, Morris SW |
| Molecular and cellular biology. 1997 ; 17 (4) : 2312-2325. |
| PMID 9121481 |
| |
| CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. |
| Stein H, Foss HD, Dˆºrkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B |
| Blood. 2000 ; 96 (12) : 3681-3695. |
| PMID 11090048 |
| |
| Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. |
| Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (9) : 1533-1559. |
| PMID 10994999 |
| |
| Anaplastic large cell lymphomas, Primary systemic (T/Null cell type). |
| Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe E |
| World Health Organization (WHO) Classification of Tumors.. |
| |
| Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma. |
| Morris SW, Xue L, Ma Z, Kinney MC |
| British journal of haematology. 2001 ; 113 (2) : 275-295. |
| PMID 11380391 |
| |
