t(2;5)(p23;q35) NPM1/ALK

2001-08-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


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.

Phenotype stem cell origin

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


Additional anomalies

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.

Genes Involved and Proteins

Gene name
ALK (anaplastic lymphoma receptor tyrosine kinase)
Protein description
after glycosylation, produces a glycoprotein; membrane associated tyrosine kinase receptor
Gene name
NPM1 (nucleophosmin)
Protein description
nuclear localisation; RNA binding nucleolar phosphoprotein involved in preribosomal assembly

Result of the Chromosomal Anomaly


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.

Expression localisation

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

Highly cited references

Pubmed IDYearTitleCitations
229123872012Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants.98
179220092007STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression.64
235688382013Cancer translocations in human cells induced by zinc finger and TALE nucleases.61
256028012015Clinical, histopathologic, and genomic features of Spitz tumors with ALK fusions.30
239999692013Novel TRAF1-ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma.29
202078482010ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions.25
195452842009Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation.21
286593372017Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene.14
325737002020IL10RA modulates crizotinib sensitivity in NPM1-ALK+ anaplastic large cell lymphoma.13
302406432018Chromosomal Translocation Formation Is Sufficient to Produce Fusion Circular RNAs Specific to Patient Tumor Cells.10
329226612020The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL).6
332460762021Minimal Residual Disease Monitoring Using a 3'ALK Universal Probe Assay in ALK-Positive Anaplastic Large-Cell Lymphoma: ddPCR, an Attractive Alternative Method to Real-Time Quantitative PCR.4
335726342021How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report.4
318046222020The mechanism of cancer drug addiction in ALK-positive T-Cell lymphoma.4
259617012015The origins of ALK translocations.3
335146572021Preclinical Evaluation of Gilteritinib on NPM1-ALK-Driven Anaplastic Large Cell Lymphoma Cells.2
324127172020Clinical, Histologic, and Molecular Characteristics of Anaplastic Lymphoma Kinase-positive Primary Cutaneous Anaplastic Large Cell Lymphoma.2
311895272019CRISPR genome editing of murine hematopoietic stem cells to create Npm1-Alk causes ALK+ lymphoma after transplantation.2
342429682021Precision therapy with anaplastic lymphoma kinase inhibitor ceritinib in ALK-rearranged anaplastic large cell lymphoma.1
306968052019CDC37 as a novel target for the treatment of NPM1-ALK expressing anaplastic large cell lymphomas.1
358072792022Synthesis of 4,5-Dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione Derivatives and Their Application as Protein Kinase Inhibitors.0
352779562022Reassessing pharmacogenomic cell sensitivity with multilevel statistical models.0
354604142022Primary Central Nervous System Anaplastic Large Cell Lymphoma, ALK Positive.0


Pubmed IDLast YearTitleAuthors
91214811997Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.Bischof D et al
90782871997Cytogenetics of lymphomas: a brief review of its theoretical and practical significance.Donner LR et al
21565481990CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.Mason DY et al
81221121994Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.Morris SW et al
113803912001Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.Morris SW et al
110900482000CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.Stein H et al
76629791995Analysis of the t(2;5)(p23;q35) translocation by reverse transcription-polymerase chain reaction in CD30+ anaplastic large-cell lymphomas, in other non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease.Wellmann A et al


Fusion gene

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
Atlas Image
t(2;5)(p23;q35) NPM1/ALK G-banding (left) [note tetraploid cells (second and third row)] and R- banding (right); - Courtesy Jean-Luc Lai and Alain Vanderhaegen; center: G-banding - Courtesy Adriana Zamecnikova. Fluorescence in situ hybridization (FISH) with Vysis ALK Break Apart probe (Abbott Molecular, US) showing rearrangement of the gene on metaphases with t(2;5)(p23;q35) (green signal on der(2) and red signal on der(5) chromosome). - Courtesy Adriana Zamecnikova.


Jean-Loup Huret

t(2;5)(p23;q35) NPM1/ALK

Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

Online version: http://atlasgeneticsoncology.org/haematological/2000/t(2;5)(p23;q35)

Historical Card

1997-12-01 t(2;5)(p23;q35) NPM1/ALK by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

1997-08-01 t(2;5)(p23;q35) NPM1/ALK by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France