BRAFV
          
            600E
           or mutant MAP2K1 human CD34+ cells establish Langerhans cell–like histiocytosis in immune-deficient mice

Rafiei, Anahita; Wilk, C. Matthias; Helbling, Patrick M.; Myburgh, Renier; Saito, Yasuyuki; Haralambieva, Eugenia; Soldini, Davide; Chakraborty, Rikhia; Mérad, Miriam; Allen, Carl E.; Nombela‐Arrieta, César; Manz, Markus G.

doi:10.1182/bloodadvances.2020001926

Cited by 6 publications

(4 citation statements)

References 24 publications

(27 reference statements)

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“…6F–J ) and spleen (Supplementary Fig. 6K–O ), revealed a strong myeloid bias (hCD33 + ) in the BRAF V600E -reconstituted mice with very low percentages of B-lymphoid (hCD19 + ) cells, similar to other comparable humanized mouse models [ 4 , 5 , 9 ]. Interestingly, a myeloid bias was also detected in the unedited (WT) fraction in mice containing BRAF V600E cells, however was not seen in mice with BRAF WT cells (Supplementary Fig.…”

Section: To the Editorsupporting

confidence: 72%

See 1 more Smart Citation

BRAFV600E promotes DC3/monocyte differentiation in human gene-engineered HSPCs and causes multisystem histiocytosis

Sconocchia,

Foßelteder,

Auinger

et al. 2023

Leukemia

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Section: To the Editorsupporting

confidence: 72%

“…Importantly, RNAseq confirmed unaltered BRAF gene expression with our approach (Fig. 1C ), representing an improvement from lentiviral-based overexpression systems, where heterologous promoters drive gene expression often from multiple viral integration sites [ 9 ].…”

Section: To the Editormentioning

confidence: 89%

BRAFV600E promotes DC3/monocyte differentiation in human gene-engineered HSPCs and causes multisystem histiocytosis

Sconocchia,

Foßelteder,

Auinger

et al. 2023

Leukemia

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“…43 HSCs carrying the BRAF V600E mutation or the mutant (c.172_186del) MAP2K1 deletion transplanted into immunodeficient MISTRG mice induce clusters of medullary, spleen, hepatic, and pulmonary cells whose morphology is that of Langerhans cells (langerine (CD207), CD1a and S100 positive with BRAF V600E mutation and without histological lesion of HCL. 44…”

Section: Cellular Origin Of Hcl?mentioning

confidence: 99%

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

2021

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Disease Overview: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment. Diagnosis: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk Stratification: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34-positive HCL cases are associated with a poor prognosis. Treatment: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/ refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or BrutonTyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future. | INTRODUCTIONHairy cell leukemia (HCL) is recognized as an entity by the World Health Organization since 2008 1 and in the last 2017 revision of the WHO classification of lymphoid neoplasms. 2 HCL, four to five times more frequent in men than women, accounts for 2% of all leukemias with approximately 1.100 new HCL cases in the United States. 3 The few available population-based studies are limited. [4][5][6][7][8] When including HCL and HCL-like disorders, the overall age-adjusted to the 2000 US population incidence rate is 0.7 per 100 000 in men and 0.3/100 000 in women. When adjusting to the worldwide population, the incidence rate of HCL is 0.3 and 0.1/100 000, respectively, and remains relatively stable over time. 8 It is lower in non-Hispanic/black, Hispanic, or Asian/pacific Islander. Despite an improvement of overall (OS) and relative survival (RS), a significantly lower OS is observed among African American individuals compared with other ethnic groups. 6 The mortality rates for patients with HCL is similar to those of the general population 5 years after diagnosis. 9 HCL must be differentiated from other

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“…HSCs carrying the BRAF V600E mutation or the mutant c.172_186del MAP2K1 deletion transplanted into immunodeficient MISTRG mice induce clusters of medullary, spleen, hepatic, and pulmonary cells whose morphology is that of Langerhans cells expressing langerine (CD207), CD1a, and S100. The BRAF V600E mutation was detected but no histological lesion of HCL was reported 107 …”

Section: What Has Recently Improved Our Understanding Of Hcl?mentioning

confidence: 99%

Hairy cell leukemia 2024: Update on diagnosis, risk‐stratification, and treatment—Annual updates in hematological malignancies

Troussard,

Maître,

Paillassa

2024

American J Hematol

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Disease OverviewHairy cell leukemia (HCL) and HCL‐like disorders, including HCL variant (HCL‐V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogenous group of mature lymphoid B‐cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.DiagnosisDiagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11c, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral bone marrow infiltration and the presence of BRAFV600E somatic mutation.Risk StratificationProgression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4‐34 positive HCL cases are associated with a poor prognosis, as well as HCL with TP53 mutations and HCL‐V.TreatmentPatients should be treated only if HCL is symptomatic. Chemotherapy with risk‐adapted therapy purine analogs (PNAs) are indicated in first‐line HCL patients. The use of chemo‐immunotherapy combining cladribine (CDA) and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus R, MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22, Bruton tyrosine kinase inhibitors (BTKi), and Bcl‐2 inhibitors (Bcl‐2i). However, the optimal sequence of the different treatments remains to be determined.

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BRAFV 600E or mutant MAP2K1 human CD34+ cells establish Langerhans cell–like histiocytosis in immune-deficient mice

Abstract: Key Points BRAFV600E or mutant MAP2K1 expression in human CB CD34+ HSPCs lead to Langerhans cell–like histiocytosis in immune-deficient mice. BRAFV600E-expressing human CB CD34+ HSPCs did not generate hairy cell leukemia in xenograft mouse models.

Cited by 6 publications

References 24 publications

BRAFV600E promotes DC3/monocyte differentiation in human gene-engineered HSPCs and causes multisystem histiocytosis

BRAFV600E promotes DC3/monocyte differentiation in human gene-engineered HSPCs and causes multisystem histiocytosis

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Hairy cell leukemia 2024: Update on diagnosis, risk‐stratification, and treatment—Annual updates in hematological malignancies

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