Translocations involving 2p23 are found in more than half cases of anaplasic large cell lymphoma (ALCL), a high grade non Hodgkin lymphoma (NHL). They involve ALK, and are therefore called ALK+ ALCL. The t(2;5) is the far most frequent 2p23 translocation in ALK+ ALCL.

T-cell in 80% (or 100%?), or null-cell type; B-cell cases, if they exist, would represent cases of large B-cell lymphomas; CD30+; present with some overlapping features with Hodgkins disease: CD30 positivity and Reed-Sternberg like cells, but the t(2;5) is not found in Hodgkins disease (it has long been debated)

10% of NHL; found in children and young adults; median around 16 yrs)

involve lymph nodes and extra nodal sites such as lungs and gastro intestinal tract

t(2;5) is found in about 30-50% of anaplastic large cell NHL (also called ALCL); it was thought previously that the t(2;5) could be found in diffuse large cell NHL or immunoblastic NHL; however, cases may easily be misdiagnosed, as the malignant cells display a pleomorphic appearance

although t(2;5) is found in aggressive high grade tumours, a 80% five yr survival seems to be associated with this anomaly

sole anomaly in less than 20% of cases; often part of a complex karyotype, with various structural and/or numerical anomalies; recurrent numerical anomalies are: +7, found in 20% of cases, +9, and +X, in 5 to 10% of cases.

closely related anomalies, also found in anaplastic large cell lymphoma, are: t(X;2)(q11;p23), t(1;2)(q25;p23), inv(2)(p23q35), t(2;3)(p23;q21), t(2;17)(p23;q23), t(2;19)(p23; p13.1) and t(2;22)(p23;q11.2). They all involve ALK in 2p23.

5 NPM-3 ALK on der(5)

2.4 kb

80 kDa; 680 amino acids; the 116 N-term aminoacids from NPM are 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.

localisation: both in the cytoplasm and in the nucleus (nucleoplasm and nucleolus)

via the kinase function activated by oligomerization of NPM-ALK mediated by the NPM part

NPM1/ALK NPM1 (5q35.1) ALK (2p23.2) COF 198 199 200 201 420 448 449 450 451 452 453 454 455 456 457 458|NPM1/ALK NPM1 (5q35.1) ALK (2p23.2) M ins(5;2)(q35;p23p23) t(2;5)(p23;q35)|NPM1/ALK NPM1 (5q35.1) ALK (2p23.2) TIC