Pediatric Hodgkin lymphoma
2023-06-25 Sheng Xiao, MD , Chunxiao Yang Affiliation1.Brigham and Women's Hospital, Harvard Medical School, Boston, MA (USA)
Classification
Definition
Pediatric Hodgkin lymphoma (HL) is a common malignancy in children, accounting for approximately 7% of childhood cancer. One of the common genomic abnormalities in HL involves the CD274/PDCD1LG2(PD-L1/PD-L2) loci at chromosome 9p24.1, which include chromosome rearrangements, small indels, mutations, copy number gains, and amplifications, leading to overexpression of PD-L1/2.1,2 PD-L1 in tumor cells binds to PD-1 in T-lymphocytes, which deactivates the cytotoxic activity of T-cells and protects tumor cells from immune attack. PD-1/PD-L1 inhibitors have been shown to be highly effective in treating patients with classic Hodgkin lymphoma (cHL) and are now the standard of care for those with relapsed or refractory cHL3. Due to the scarcity of tumor cells in HL, with typically less than 1% of the tumor mass consisting of Reed-Sternberg (RS) cells or lymphocyte-predominant (LP) cells, obtaining a genomic profile requires enrichment of tumor cells by laser capture microdissection or flow cytometry/fluorescence-activated cell sorting. Therefore, routine clinical testing for genomic aberrations in HL remains challenging.
| Pediatric Hodgkin lymphoma | Genetic marker(s) |
|---|---|
| Classic Hodgkin lymphoma | Most common mutations in cHL include CD274(PD-L1)/PDCD1LG2(PD-L2), STAT6 (JAK-STAT signaling), ITPKB (PI3K/AKT/mTOR signaling), TNFAIP3( NF-κB signaling), and B2M.4 The truncation of the 3′-untranslated region (3'-UTR) of the CD274, caused by translocations, inversions, small deletions, or small tandem duplications, is the most common genomic change leading to the PD-L1 overexpression. PD-L1 3'-UTR has a negative regulatory role in mRNA stability, therefore, the loss of 3'-UTR results in the increased shell life of PD-L1 transcript. 5 These patients are sensitive to PD-1/PD-L1 inhibition. |
| Nodular lymphocyte-predominant Hodgkin lymphoma | NLPHL is characterized by the clonal proliferation of B-cells derived from germinal centers that remain within a follicular environment. The mutation profile of the nodular lymphocyte-predominant Hodgkin lymphoma overlaps with that of DLBCL and cHL. Most common mutations in NLPHL include SOCS1, JUNB, DUSP2, SGK1, CREBBP, PIM1, PAX5, RHOH, MYC, BCL6, CD274, and PDCD1LG2. Additional frequently mutated genes include ZFP36L1, CARD11, TNFAIP3, NFKBIA, CDKN2A, REL, BCL11A, BCL6, CARD11, JAK2, and ATM . Additional chromosome aberrations include t(3;14)(q27;q32); 9p24 rearrangement.6-10 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 34520052 | 2022 | 9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial. | Gerhard-Hartmann E et al |
| 2 | 33567641 | 2021 | Genomic Landscape of Hodgkin Lymphoma. | Brune MM et al |
| 3 | 33439697 | 2021 | PD-1 Blockade in Classic Hodgkin Lymphoma. | Ansell SM et al |
| 4 | 23867303 | 2014 | The microenvironment in classical Hodgkin lymphoma: an actively shaped and essential tumor component. | Liu Y et al |
| 5 | 29394125 | 2018 | Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma. | Roemer MGM et al |
| 6 | 16614247 | 2006 | Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma. | Liso A et al |
| 7 | 17652621 | 2007 | Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6. | Mottok A et al |
| 8 | 26658840 | 2016 | Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma. | Hartmann S et al |
| 9 | 30213827 | 2019 | JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte-rich large B-cell lymphoma. | Schuhmacher B et al |
| 10 | 12393409 | 2003 | Frequent occurrence of BCL6 rearrangements in nodular lymphocyte predominance Hodgkin lymphoma but not in classical Hodgkin lymphoma. | Wlodarska I et al |
Citation
Sheng Xiao, MD ; Chunxiao Yang
Pediatric Hodgkin lymphoma
Atlas Genet Cytogenet Oncol Haematol. 2023-06-25
Online version: http://atlasgeneticsoncology.org/solid-tumor/209183/pediatric-hodgkin-lymphoma
