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On flow cytometry, HCL cells express brightly mature B-lymphoid cell antigens as CD19, CD20, CD22, CD200, are typically positive for CD11c, CD103, CD123 and CD25, while are usually negative or dim for CD5, CD23, CD10, CD79b and CD27. Three cases (3/71, 4%) - despite expressing CD25, CD11c, and CD200 on all clonal cells (which were 15%, 22% and 37% of total leukocytes, respectively) - had CD103 expressed only on a fraction of leukaemic cells (40%, 27%, and 10.8%, corresponding to 5%, 6% and 4% of total leukocytes) (Figure 1A). Keywords: CD103; flow cytometry; hairy cell leukaemia EN CD103 flow cytometry hairy cell leukaemia e28 e31 4 07/18/22 20220715 NES 220715 Classical hairy cell leukaemia (HCLc) is an uncommon mature B-cell lymphoproliferative neoplasm (MBCLN) comprising about 2% of lymphoid leukaemias. [Extracted from the article]

The article highlights hairy-cell leukemia which is a rare chronic B-cell neoplasm. Treatment included are use of purine analogues such as cladribine or pentostatin, targeted therapy with the BRAF inhibitor vemurafenib in combination with anti-CD20 rituximab immunotherapy which suggests that venetoclax may be a promising treatment option for hairy-cell leukemia, especially in patients who have failed other therapies.

Clonal hematopoiesis predisposes to hematological malignancies. However, clonal hematopoiesis is understudied in classical Hodgkin lymphoma (cHL), a mature B-cell neoplasm exhibiting the most abundant microenvironment. We analyzed clonal hematopoiesis in 40 cHL cases by sequencing microdissected tumor cells and matched normal cells from blood and/or lymph nodes. Five patients had blood and/or tissue clonal hematopoiesis. In three of five patients (all failing first-line therapy), clonal hematopoiesis spread through the tissue microenvironment extensively, and featured mutant DNMT3A R882H , KRAS G60D and DNMT3A R882H + TET2 Q1274 * in 33%, 92% and 60% of non-neoplastic cells, respectively. In the latter case, DNMT3A/TET2- mutant clonal hematopoiesis seeded the neoplastic clone, which was infected by the Epstein-Barr virus and showed almost no other somatic mutations exome-wide. In the former case, DNMT3A -mutant clonal hematopoiesis did not originate the neoplastic clone despite dominating the blood and B-cell lineage (~94% leukocytes; ~96% mature blood B cells), yet led to NPM1 -mutated acute myeloid leukemia 6 years after therapy for cHL. Our results expand to cHL the spectrum of hematologic malignancies associated with clonal hematopoiesis., Competing Interests: Conflict of interest: M.P. Martelli reports personal fees from AbbVie, Amgen, Pfizer, Jazz Pharmaceuticals, Novartis, and Janssen outside the submitted work. The authors declare no potential conflicts of interest.

The BRAF-V600E mutation defines genetically hairy cell leukemia among B-cell leukemias and lymphomas. In solid tumors, BRAF-V600E is known to aberrantly activate the oncogenic MEK-ERK pathway, and targeted BRAF and/or MEK inhibitors have shown remarkable efficacy in clinical trials in melanoma patients. However, the MEK-ERK pathway status in hairy cell leukemia has not been thoroughly investigated. We assessed phospho-ERK expression in 37 patients with hairy cell leukemia and 44 patients with neoplasms mimicking hairy cell leukemia (40 splenic marginal zone lymphoma, 2 hairy cell leukemia-variant and 2 splenic lymphoma/leukemia unclassifiable) using immunohistochemistry on routine biopsies and/or Western blotting on purified leukemic cells, and correlated the phospho-ERK status with the BRAF-V600E mutation status. Besides confirming the constant presence of BRAF-V600E in all patients with hairy cell leukemia, we observed ubiquitous phospho-ERK expression in this malignancy. Conversely, all 44 cases with neoplasms mimicking hairy cell leukemia were devoid of BRAF-V600E and none expressed phospho-ERK. Furthermore, the two exceptionally rare cases of non-hairy cell leukemia unclassifiable chronic B-cell neoplasms previously reported to be BRAF-V600E(+) on allele-specific polymerase chain reaction lacked phospho-ERK expression as well, suggesting the presence of the mutation in only a small part of the leukemic clone in these cases. In conclusion, our findings support the use of phospho-ERK immunohistochemistry in the differential diagnosis between hairy cell leukemia and its mimics, and establish the MEK-ERK pathway as a rational therapeutic target in this malignancy.