5q35.1

B23,NPM

Anaplasic large cell lymphoma (ALCL) with t(2;5)(p23;q35) --> NPM1- ALK

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)

nonetheless, a 80% five yr survival may be associated with this anomaly

additional anomalies are most often found

5 NPM1-3 ALK on der(5)

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.

via the kinase function activated by oligomerization of NPM1-ALK mediated by the NPM1 part

t(3;5)(q25;q34)/in myeloid malignancies --> NPM1 - MLF1

Acute non lymphocytic leukemia (AML), myelodysplasia (MDS), chronic myelogenous leukemia in blast crisis (BC-CML); trilineage involvement

very poor

location of breakpoints difficult to ascertain

5 NPM-3 MLF1 on der(5)

with the 175 N term amino acids of NPM1; nuclear protein

t(5;17)(q34;q21)/M3-AML --> NPM1-RARa

promyelocytic AML (M3-AML)

variant translocation of the well known t(15;17)

5 NPM1-3 RARa on der(5)

with the 117 N term amino acids of NPM1