Cutaneous Manifestations of Myeloid Neoplasms Exhibit Broad and Divergent Morphologic and Immunophenotypic Features but Share Ancestral Clonal Mutations With Bone Marrow

Sadigh, Sam; DeAngelo, Daniel J.; Garcia, Jacqueline S.; Hasserjian, Robert P.; Hergott, Christopher B.; Lane, Andrew A.; Lovitch, Scott B.; Lucas, Fabienne; Luskin, Marlise R.; Morgan, Elizabeth A.; Pinkus, Geraldine S.; Pozdnyakova, Olga; Rodig, Scott J.; Shanmugam, Vignesh; Tsai, Harrison K.; Winer, Eric S.; Zemmour, David; Kim, Annette S.

doi:10.1016/j.modpat.2023.100352

Cited by 2 publications

(2 citation statements)

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“…As mutated TET2 is considered a common agedependent clonal hematopoiesis mutation with increasing frequency at older age (11) and older patients have UV exposure accumulation throughout their life (17,18), our findings are consistent with UV exposure and mutated TET2 as a combined aging-associated mechanism of BPDCN oncogenesis in older patients, particularly in those presenting with skin only disease. As skin involvement is also seen in other myeloid neoplasms (19), future research might evaluate the role of UV radiation in these cases well. On the other hand, systemic involvement was associated with NRAS mutations and higher rates of complex karyotype.…”

Section: Discussionmentioning

confidence: 99%

“…After a median follow-up of 41.6 months (95% CI 28-81), the median OS was 18.2 months (95% CI [13][14][15][16][17][18][19][20][21][22][23][24]. When evaluated by organ involvement group, the median OS was 23.5 months (95% CI 13.4-NA) in the skin only group, 20.4 months (95% CI 10.6-25.6) in the skin plus systemic group (p=0.3 compared to skin only group) and 17.5 months (95% CI 9.0-22.1) in the systemic only group (p=0.066 vs. skin only group) (Figure 4A).…”

Section: Survivalmentioning

confidence: 99%

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Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival

Shimony,

Keating,

Fay

et al. 2024

Blood Advances

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) can involve skin, bone marrow (BM), central nervous system (CNS), and non-CNS extramedullary sites. Preclinical models demonstrated clonal advantage of TET2-mutated plasmacytoid dendritic cells exposed to UV radiation. However, whether sun exposure, disease characteristics, and patient survival are clinically related is unclear. We classified 66 BPDCN patients based on organ involvement at diagnosis as skin only (n=19), systemic plus skin (n=33), or systemic only (n=14). BM involvement was absent, microscopic (<5%), or overt (≥5%). UV exposure history was based on clinical and demographic data. Patients with skin only BPDCN were more frequently ≥75 years (47% vs. 19%, p=0.032) and had lower rates of complex karyotype (0 vs. 32%, p=0.022) and mutated NRAS (0 vs. 29%, p=0.044). Conversely, those in the systemic only group had lower UV exposure (23% vs. 59%, p=0.03) and fewer TET2 mutations (33% vs. 72%, p=0.051). With median follow-up of 42 months, the median overall survival (OS) was 23.5, 20.4, and 17.5 months for skin only, systemic plus skin, and systemic only, respectively. Patients with no BM involvement had better OS vs. overt BM involvement (median OS 27.3 vs. 15.0 months, p=0.033) and comparable to those with microscopic BM involvement (27.3 vs. 23.5 months, p=0.6). Overt BM involvement remained significant for OS in a multivariable analysis adjusted for baseline characteristics and treatment. In summary, BPDCN clinical characteristics are associated with disease genetics and survival. These data are useful to estimate prognosis for individual patients and may indicate informative subtyping of BPDCN.

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Section: Discussionmentioning

confidence: 99%

Section: Survivalmentioning

confidence: 99%

Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival

Shimony,

Keating,

Fay

et al. 2024

Blood Advances

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Cutaneous Langerhans cell histiocytosis and other systemic inflammatory or autoimmune disease manifestations in the setting of clonal hematopoiesis

George,

Liesveld,

El Hussein

et al. 2024

eJHaem

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The clinical manifestations and pathophysiology of clonal hematopoiesis (CH)‐associated immunological dysfunction are poorly understood. We describe an elderly woman with CH who developed various systemic inflammatory or autoimmune diseases (SIADs), including cutaneous Langerhans cell histiocytosis (LCH) and temporal arteritis. Sequencing of the LCH revealed somatic oncogenic mutations in MAP2K1, IDH2, and SRSF2, with enrichment of the latter two in her peripheral blood at high allele frequencies. These findings raise concern for the future development of a myeloid malignancy. Given the mounting evidence for adult‐onset autoinflammatory conditions caused by somatic blood mutations, we suspect CH‐mediated immune dysregulation is contributing to her multi‐organ involvement by a combination of SIADs.

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Cutaneous Manifestations of Myeloid Neoplasms Exhibit Broad and Divergent Morphologic and Immunophenotypic Features but Share Ancestral Clonal Mutations With Bone Marrow

Cited by 2 publications

References 63 publications

Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival

Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival

Cutaneous Langerhans cell histiocytosis and other systemic inflammatory or autoimmune disease manifestations in the setting of clonal hematopoiesis

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