Martina Carlotti | Université de Bordeaux (original) (raw)

Papers by Martina Carlotti

Annales De Dermatologie Et De Venereologie, Dec 1, 2013

Annales De Dermatologie Et De Venereologie, Dec 1, 2013

JDP 2013 fonction des coupes. Nous émettons l'hypothèse que les histiocytes spumeux seraient plus... more JDP 2013 fonction des coupes. Nous émettons l'hypothèse que les histiocytes spumeux seraient plus fréquemment associés à la MFF que ne le laisse supposer la littérature. Conclusion.-Nous soulignons dans cette observation l'importance de la xanthomatose péricanalaire comme une clé pour le diagnostic de la maladie de Fox-Fordyce. Déclaration d'intérêt.-Aucun.

Journal of Investigative Dermatology, 2010

Frontiers in Oncology, 2021

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL) in wh... more Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL) in which the human Telomerase Reverse Transcriptase (hTERT) gene is re-expressed. Current available treatments do not provide long-term response. We previously reported that Histone deacetylase inhibitors (HDACi, romidespin and vorinostat) and a DNA methyltransferase inhibitor (DNMTi, 5-azacytidine) can reduce hTERT expression without altering the methylation level of hTERT promoter. Romidepsin and vorinostat are approved for CTCL treatment, while 5-azacytidine is approved for the treatment of several hematological disorders, but not for CTCL. Here, using the soft agar assay, we analyzed the functional effect of the aforementioned epidrugs on the clonogenic capacities of Sézary cells. Our data revealed that, besides hTERT downregulation, epidrugs’ pressure reduced the proliferative and the tumor formation capacities in Sézary cells in vitro.

Modern Pathology, 2010

Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign ... more Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (AÀ) or 'favor malignant' (A þ). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.

Journal of Investigative Dermatology, 2010

The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of c... more The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of cutaneous anaplastic large cell lymphomas (C-ALCLs) (Leukemia, 2009; 23(3):574-80) prompted us to study IRF4 locus status in different cutaneous T-cell lymphoma (CTCL) subtypes. Fluorescence in situ hybridization (FISH) was used with break-apart dual-color probes. Sixty samples from 54 patients were analyzed with 23 C-ALCL, 11 transformed mycosis fungoides (T-MF), 7 lymphomatoid papulosis (LyP), and 13 Sé zary syndrome (SS) cases. IRF4 immunostaining was performed in 32 cases. We observed a split FISH signal pattern indicating a translocation at the IRF4 locus in 6 out of 23 C-ALCL (26%) and 2 out of 11 T-MF (18.2%) cases. Extra copies of the IRF4 locus were found in 4 out of 13 SS, 1 out of 11 T-MF, and 1 out of 23 C-ALCL cases, corresponding to either aneuploidy, chromosome 6 trisomy, or 6p partial gain. The IRF4 expression was not correlated with the presence of IRF4 alteration in C-ALCL or T-MF. Interestingly, IRF4 rearrangements define a subgroup of CD30-positive C-ALCL and T-MF cases. Conversely, T-MF cases with IRF4 rearrangements may correspond to the development of C-ALCL in MF patients and not to large cell transformation. Investigation of the biological pathways triggered by IRF4 rearrangements and/or expression in CTCL will provide a biological basis for IRF4-directed therapy.

Journal of Investigative Dermatology, 2010

Impaired invariant chain degradation and antigen presentation and diminished collagen-induced art... more Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity 10:207-17 Namer B, Carr R, Johanek LM et al. (2008) Separate peripheral pathways for pruritus in man. J Neurophysiol 100:2062-9 Oikonomopoulou K, Hansen KK, Saifeddine M et al. (2006) Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs). Biol Chem 387:817-24 Reddy VB, Iuga AO, Shimada S et al. (2008) Cowhage evoked itch is mediated by a novel cysteine protease-a ligand of protease activated receptors. J Neurosci 28:4331-5 Schwarz G, Boehncke WH, Braun M et al. (2002) Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-g. J Invest Dermatol 119:44-9

American Journal of Surgical Pathology, 2013

Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transfor... more Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transformation in about 10% of cases. Transformed mycosis fungoides (T-MF) is often associated with the appearance of a CD20 component. The aim of this study was to analyze whether such cells are reactive or lymphomatous and to evaluate their prognostic impact. Among 311 T-MFs from the French Cutaneous Lymphoma Study Group registry, we studied 148 cases. CD20 was expressed in 88 cases (59%). The proportion of CD20 cells among T-MF lesions was <10% for 54 cases (38%), 10% to 49% for 71 cases (81%), and >50% for 17 cases (19%). We focused the study on 23 cases that contained >50% CD20 cells. To evaluate the nature of the CD20 component, we used immunohistochemistry (2 anti-CD20 antibodies, L26 and 7D1 clones, and 2 other anti-B-cell antigen antibodies, CD22 and PAX5) and a double-stain immunofluorescence technique (anti-CD20 and anti-CD3 antibodies). The clonality of B cells was studied by polymerase chain reaction. Three profiles were observed. In 15 of the 23 cases, the CD20 cells were reactive. In 6 cases, CD20 protein was aberrantly expressed in T-MF lesions. Lastly, there were 2 composite lymphomas (T-MF infiltrate with a B-cell follicular lymphoma). In view of this series, we propose a simple algorithm to help pathologists evaluate the nature of the CD20 component associated with T-MF. Although statistically not significant, there was a trend toward a worse prognosis in the presence of >50% CD20 cells and of a nodular perifollicular pattern of this component.

Hematological Oncology, 2017

cating regions of the genome. 166 Kataegis-ROIs were identified, 42/64/17/4 of which were known t... more cating regions of the genome. 166 Kataegis-ROIs were identified, 42/64/17/4 of which were known targets of aberrant somatic hypermutation (SHM) / were located within the immunoglobulin (IG) loci / overlapped with lymphoma-associated genes / overlapped with cancer genes known from other entities, respectively. Kataegis-ROIs were enriched in early replicating regions of the genome. In an analysis of mutational signatures, 11 known signatures including clocklike signatures (e.g. spontaneous deamination), DNA repair defect signatures, an APOBEC signature and the B-cell specific signature AC9 (attributed to AID and polymerase η) were found. Furthermore, we discovered three new signatures (L1-L3). L1 was enriched at the IG loci. L2 was specifically enriched in the constant domains of the IGH locus. Conclusions: L1 and L2 may be interpreted as an imprint of the action of AID on the genome, L2 with a high amount of modulation by altered repair pathways, L1 with a lower amount of modulation. Both L1 and L2 contribute to SHM, whereas class switch recombination (CSR) may be explained with only L1. Kataegis clusters may be classified into two groups, one of which is attributable to aberrant SHM, the other to dysregulated CSR.

Annales de Dermatologie et de Vénéréologie, 2011

Communications orales A95 Discussion.-Il s'agit de la première série française de lymphomes anapl... more Communications orales A95 Discussion.-Il s'agit de la première série française de lymphomes anaplasiques CD30+ cutanés primitifs chez l'enfant immunocompétent. Il s'agit de 3 garçons et 2 filles, l'âge moyen lors de diagnostic étant de 11,6 (7-16) ans. Le diagnostic de pC-ALCL était établi au terme d'une discussion collégiale sur des critères cliniques, histologiques, immunohistochimiques et en biologie moléculaire, après exclusion des diagnostics différentiels. Les lymphomes anaplasiques CD30+ extra-cutanés chez l'enfant sont des formes systémiques agressives nécessitant une chimiothérapie. Notre série de cas illustre l'évolution clinique favorable des pC-ALCL chez l'enfant, malgré une présentation clinique et histologique parfois inquiétante. Aucun de nos patients n'a présenté d'évolution systémique après un suivi de 13 mois à 9 ans. Conclusion.-Les lymphomes anaplasiques CD30+ primitivement cutanés chez l'enfant immunocompétent constituent une entité distincte de bon pronostic, ne relevant pas d'une chimiothérapie agressive. Déclaration d'intérêts.-Aucun.

Annales de Dermatologie et de Vénéréologie

Introduction Le syndrome de Sezary (SS) est un lymphome T cutane caracterise par un clone T domin... more Introduction Le syndrome de Sezary (SS) est un lymphome T cutane caracterise par un clone T dominant circulant et une infiltration cutanee associee a une erythrodermie et un prurit. Les mecanismes controlant la migration entre les compartiments sanguin et cutane sont mal connus, expliquant le manque de traitements efficaces. Des etudes anterieures nous ont amenees a etudier l’expression et la fonction du chimiorecepteur CXCR4 dans le SS. Materiel et methodes Sur une cohorte de 21 patients atteints de SS, nous avons quantifie l’expression de CXCR4 a la surface des cellules de Sezary circulantes par cytometrie multicouleur, et compare ces resultats aux donnees cliniques des patients. Les proprietes migratoires des cellules en reponse au chimioattractant de CXCR4 (SDF-1) ont ete etudiees in vitro, en presence d’un antagoniste de CXCR4 (AMD3100) ou d’un anticorps (Ac) anti-CXCR4. Le role de CXCR4 dans la survie des cellules de Sezary a ete explore par test d’apoptose-necrose apres traitement des cellules par AMD3100 ou Ac anti-CXCR4. Enfin, nous avons construit un shARN inhibant l’expression de CXCR4 afin de transduire des cellules de Sezary de patients et de confirmer son role fonctionnel in vivo apres injection chez la souris. Resultats La majorite des cellules de Sezary des 21 patients exprimaient fortement CXCR4 (pourcentage median de cellules CXCR4+ = 96,9 ± 9,6 %), et ce de facon homogene entre les patients. Le niveau d’expression de CXCR4 etait independant des principaux facteurs pronostiques de la maladie. L’AMD3100 et l’Ac anti-CXCR4 bloquaient significativement la migration des cellules de Sezary en reponse a SDF-1 (taux d’inhibition respectifs = 90,6 ± 5,6 % et 60,8 ± 16,4 %, p Discussion Le role fonctionnel de CXCR4 que nous decrivons sur les cellules de patients n’a pas ete valide avec la lignee HUT78 (SS). Ceci suggere que CXCR4 pourrait avoir des conformations differentes selon les cellules ce qui affecterait sa fonction. La validation de ces resultats dans un modele de xenogreffe de cellules de Sezary modifiees avec un shARN inhibant l’expression de CXCR4 permettra de determiner si son inhibition est une strategie therapeutique impactant la survie et/ou la dissemination des cellules tumorales. Conclusion La forte proportion de cellules CXCR4+ dans le SS et la preuve fonctionnelle de son implication dans la migration cellulaire et la survie des cellules in vitro font de CXCR4 une cible therapeutique potentielle.

European Journal of Cancer

European Journal of Cancer

European Journal of Cancer

Blood Advances

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes (LN) as densely packed agg... more Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes (LN) as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. In vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B-cell lymphomas remain scarce, while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on cell encapsulation inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating lymphoma B cells, extracellular matrix (ECM), and/or tonsil stromal cells (TSC). We revealed that under 3D confinement lymphoma B cells were able to form cohesive spheroids resulting from overexpression of ECM components. Moreover, lymphoma B cells and TSC dynamically formed self-organized 3D spheroids favoring spheroid growth. 3D culture induced resistance to classical c...

Leukemia

Sézary Syndrome (SS) is a rare aggressive epidermotropic cutaneous T-cell lymphoma (CTCL) defined... more Sézary Syndrome (SS) is a rare aggressive epidermotropic cutaneous T-cell lymphoma (CTCL) defined by erythroderma, pruritis, and a circulating atypical CD4 + T-cell clonal population. The diversity of Sézary cell (SC) phenotype and genotype may reflect either plasticity or heterogeneity, which was difficult to evaluate dynamically until the achievement of long-term SC expansion. Therefore, we developed six defined culture conditions allowing for the expansion of SC defined by their phenotype and monoclonality in four of seven SS cases. Engraftment of SC through the intrafemoral route into immunodeficient NOD.Cg-Prkdc(scid)Il2rg(tm1Wjll)/SzJ (NSG) mice was achieved in 2 of 14 SS cases. Secondary xenograft by percutaneous injection mimicked most of the features of SS with dermal infiltration, epidermotropism, and blood spreading. These models also allowed assessing the intra-individual heterogeneity of patient SC. Subclones sharing the same TCR gene rearrangement evolved independently...

Cancer Medicine

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The American Journal of Surgical Pathology

Annales De Dermatologie Et De Venereologie, Dec 1, 2013

Annales De Dermatologie Et De Venereologie, Dec 1, 2013

JDP 2013 fonction des coupes. Nous émettons l'hypothèse que les histiocytes spumeux seraient plus... more JDP 2013 fonction des coupes. Nous émettons l'hypothèse que les histiocytes spumeux seraient plus fréquemment associés à la MFF que ne le laisse supposer la littérature. Conclusion.-Nous soulignons dans cette observation l'importance de la xanthomatose péricanalaire comme une clé pour le diagnostic de la maladie de Fox-Fordyce. Déclaration d'intérêt.-Aucun.

Journal of Investigative Dermatology, 2010

Frontiers in Oncology, 2021

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL) in wh... more Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL) in which the human Telomerase Reverse Transcriptase (hTERT) gene is re-expressed. Current available treatments do not provide long-term response. We previously reported that Histone deacetylase inhibitors (HDACi, romidespin and vorinostat) and a DNA methyltransferase inhibitor (DNMTi, 5-azacytidine) can reduce hTERT expression without altering the methylation level of hTERT promoter. Romidepsin and vorinostat are approved for CTCL treatment, while 5-azacytidine is approved for the treatment of several hematological disorders, but not for CTCL. Here, using the soft agar assay, we analyzed the functional effect of the aforementioned epidrugs on the clonogenic capacities of Sézary cells. Our data revealed that, besides hTERT downregulation, epidrugs’ pressure reduced the proliferative and the tumor formation capacities in Sézary cells in vitro.

Modern Pathology, 2010

Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign ... more Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (AÀ) or 'favor malignant' (A þ). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.

Journal of Investigative Dermatology, 2010

The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of c... more The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of cutaneous anaplastic large cell lymphomas (C-ALCLs) (Leukemia, 2009; 23(3):574-80) prompted us to study IRF4 locus status in different cutaneous T-cell lymphoma (CTCL) subtypes. Fluorescence in situ hybridization (FISH) was used with break-apart dual-color probes. Sixty samples from 54 patients were analyzed with 23 C-ALCL, 11 transformed mycosis fungoides (T-MF), 7 lymphomatoid papulosis (LyP), and 13 Sé zary syndrome (SS) cases. IRF4 immunostaining was performed in 32 cases. We observed a split FISH signal pattern indicating a translocation at the IRF4 locus in 6 out of 23 C-ALCL (26%) and 2 out of 11 T-MF (18.2%) cases. Extra copies of the IRF4 locus were found in 4 out of 13 SS, 1 out of 11 T-MF, and 1 out of 23 C-ALCL cases, corresponding to either aneuploidy, chromosome 6 trisomy, or 6p partial gain. The IRF4 expression was not correlated with the presence of IRF4 alteration in C-ALCL or T-MF. Interestingly, IRF4 rearrangements define a subgroup of CD30-positive C-ALCL and T-MF cases. Conversely, T-MF cases with IRF4 rearrangements may correspond to the development of C-ALCL in MF patients and not to large cell transformation. Investigation of the biological pathways triggered by IRF4 rearrangements and/or expression in CTCL will provide a biological basis for IRF4-directed therapy.

Journal of Investigative Dermatology, 2010

Impaired invariant chain degradation and antigen presentation and diminished collagen-induced art... more Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity 10:207-17 Namer B, Carr R, Johanek LM et al. (2008) Separate peripheral pathways for pruritus in man. J Neurophysiol 100:2062-9 Oikonomopoulou K, Hansen KK, Saifeddine M et al. (2006) Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs). Biol Chem 387:817-24 Reddy VB, Iuga AO, Shimada S et al. (2008) Cowhage evoked itch is mediated by a novel cysteine protease-a ligand of protease activated receptors. J Neurosci 28:4331-5 Schwarz G, Boehncke WH, Braun M et al. (2002) Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-g. J Invest Dermatol 119:44-9

American Journal of Surgical Pathology, 2013

Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transfor... more Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transformation in about 10% of cases. Transformed mycosis fungoides (T-MF) is often associated with the appearance of a CD20 component. The aim of this study was to analyze whether such cells are reactive or lymphomatous and to evaluate their prognostic impact. Among 311 T-MFs from the French Cutaneous Lymphoma Study Group registry, we studied 148 cases. CD20 was expressed in 88 cases (59%). The proportion of CD20 cells among T-MF lesions was <10% for 54 cases (38%), 10% to 49% for 71 cases (81%), and >50% for 17 cases (19%). We focused the study on 23 cases that contained >50% CD20 cells. To evaluate the nature of the CD20 component, we used immunohistochemistry (2 anti-CD20 antibodies, L26 and 7D1 clones, and 2 other anti-B-cell antigen antibodies, CD22 and PAX5) and a double-stain immunofluorescence technique (anti-CD20 and anti-CD3 antibodies). The clonality of B cells was studied by polymerase chain reaction. Three profiles were observed. In 15 of the 23 cases, the CD20 cells were reactive. In 6 cases, CD20 protein was aberrantly expressed in T-MF lesions. Lastly, there were 2 composite lymphomas (T-MF infiltrate with a B-cell follicular lymphoma). In view of this series, we propose a simple algorithm to help pathologists evaluate the nature of the CD20 component associated with T-MF. Although statistically not significant, there was a trend toward a worse prognosis in the presence of >50% CD20 cells and of a nodular perifollicular pattern of this component.

Hematological Oncology, 2017

cating regions of the genome. 166 Kataegis-ROIs were identified, 42/64/17/4 of which were known t... more cating regions of the genome. 166 Kataegis-ROIs were identified, 42/64/17/4 of which were known targets of aberrant somatic hypermutation (SHM) / were located within the immunoglobulin (IG) loci / overlapped with lymphoma-associated genes / overlapped with cancer genes known from other entities, respectively. Kataegis-ROIs were enriched in early replicating regions of the genome. In an analysis of mutational signatures, 11 known signatures including clocklike signatures (e.g. spontaneous deamination), DNA repair defect signatures, an APOBEC signature and the B-cell specific signature AC9 (attributed to AID and polymerase η) were found. Furthermore, we discovered three new signatures (L1-L3). L1 was enriched at the IG loci. L2 was specifically enriched in the constant domains of the IGH locus. Conclusions: L1 and L2 may be interpreted as an imprint of the action of AID on the genome, L2 with a high amount of modulation by altered repair pathways, L1 with a lower amount of modulation. Both L1 and L2 contribute to SHM, whereas class switch recombination (CSR) may be explained with only L1. Kataegis clusters may be classified into two groups, one of which is attributable to aberrant SHM, the other to dysregulated CSR.

Annales de Dermatologie et de Vénéréologie, 2011

Communications orales A95 Discussion.-Il s'agit de la première série française de lymphomes anapl... more Communications orales A95 Discussion.-Il s'agit de la première série française de lymphomes anaplasiques CD30+ cutanés primitifs chez l'enfant immunocompétent. Il s'agit de 3 garçons et 2 filles, l'âge moyen lors de diagnostic étant de 11,6 (7-16) ans. Le diagnostic de pC-ALCL était établi au terme d'une discussion collégiale sur des critères cliniques, histologiques, immunohistochimiques et en biologie moléculaire, après exclusion des diagnostics différentiels. Les lymphomes anaplasiques CD30+ extra-cutanés chez l'enfant sont des formes systémiques agressives nécessitant une chimiothérapie. Notre série de cas illustre l'évolution clinique favorable des pC-ALCL chez l'enfant, malgré une présentation clinique et histologique parfois inquiétante. Aucun de nos patients n'a présenté d'évolution systémique après un suivi de 13 mois à 9 ans. Conclusion.-Les lymphomes anaplasiques CD30+ primitivement cutanés chez l'enfant immunocompétent constituent une entité distincte de bon pronostic, ne relevant pas d'une chimiothérapie agressive. Déclaration d'intérêts.-Aucun.

Annales de Dermatologie et de Vénéréologie

Introduction Le syndrome de Sezary (SS) est un lymphome T cutane caracterise par un clone T domin... more Introduction Le syndrome de Sezary (SS) est un lymphome T cutane caracterise par un clone T dominant circulant et une infiltration cutanee associee a une erythrodermie et un prurit. Les mecanismes controlant la migration entre les compartiments sanguin et cutane sont mal connus, expliquant le manque de traitements efficaces. Des etudes anterieures nous ont amenees a etudier l’expression et la fonction du chimiorecepteur CXCR4 dans le SS. Materiel et methodes Sur une cohorte de 21 patients atteints de SS, nous avons quantifie l’expression de CXCR4 a la surface des cellules de Sezary circulantes par cytometrie multicouleur, et compare ces resultats aux donnees cliniques des patients. Les proprietes migratoires des cellules en reponse au chimioattractant de CXCR4 (SDF-1) ont ete etudiees in vitro, en presence d’un antagoniste de CXCR4 (AMD3100) ou d’un anticorps (Ac) anti-CXCR4. Le role de CXCR4 dans la survie des cellules de Sezary a ete explore par test d’apoptose-necrose apres traitement des cellules par AMD3100 ou Ac anti-CXCR4. Enfin, nous avons construit un shARN inhibant l’expression de CXCR4 afin de transduire des cellules de Sezary de patients et de confirmer son role fonctionnel in vivo apres injection chez la souris. Resultats La majorite des cellules de Sezary des 21 patients exprimaient fortement CXCR4 (pourcentage median de cellules CXCR4+ = 96,9 ± 9,6 %), et ce de facon homogene entre les patients. Le niveau d’expression de CXCR4 etait independant des principaux facteurs pronostiques de la maladie. L’AMD3100 et l’Ac anti-CXCR4 bloquaient significativement la migration des cellules de Sezary en reponse a SDF-1 (taux d’inhibition respectifs = 90,6 ± 5,6 % et 60,8 ± 16,4 %, p Discussion Le role fonctionnel de CXCR4 que nous decrivons sur les cellules de patients n’a pas ete valide avec la lignee HUT78 (SS). Ceci suggere que CXCR4 pourrait avoir des conformations differentes selon les cellules ce qui affecterait sa fonction. La validation de ces resultats dans un modele de xenogreffe de cellules de Sezary modifiees avec un shARN inhibant l’expression de CXCR4 permettra de determiner si son inhibition est une strategie therapeutique impactant la survie et/ou la dissemination des cellules tumorales. Conclusion La forte proportion de cellules CXCR4+ dans le SS et la preuve fonctionnelle de son implication dans la migration cellulaire et la survie des cellules in vitro font de CXCR4 une cible therapeutique potentielle.

European Journal of Cancer

European Journal of Cancer

European Journal of Cancer

Blood Advances

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes (LN) as densely packed agg... more Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes (LN) as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. In vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B-cell lymphomas remain scarce, while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on cell encapsulation inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating lymphoma B cells, extracellular matrix (ECM), and/or tonsil stromal cells (TSC). We revealed that under 3D confinement lymphoma B cells were able to form cohesive spheroids resulting from overexpression of ECM components. Moreover, lymphoma B cells and TSC dynamically formed self-organized 3D spheroids favoring spheroid growth. 3D culture induced resistance to classical c...

Leukemia

Sézary Syndrome (SS) is a rare aggressive epidermotropic cutaneous T-cell lymphoma (CTCL) defined... more Sézary Syndrome (SS) is a rare aggressive epidermotropic cutaneous T-cell lymphoma (CTCL) defined by erythroderma, pruritis, and a circulating atypical CD4 + T-cell clonal population. The diversity of Sézary cell (SC) phenotype and genotype may reflect either plasticity or heterogeneity, which was difficult to evaluate dynamically until the achievement of long-term SC expansion. Therefore, we developed six defined culture conditions allowing for the expansion of SC defined by their phenotype and monoclonality in four of seven SS cases. Engraftment of SC through the intrafemoral route into immunodeficient NOD.Cg-Prkdc(scid)Il2rg(tm1Wjll)/SzJ (NSG) mice was achieved in 2 of 14 SS cases. Secondary xenograft by percutaneous injection mimicked most of the features of SS with dermal infiltration, epidermotropism, and blood spreading. These models also allowed assessing the intra-individual heterogeneity of patient SC. Subclones sharing the same TCR gene rearrangement evolved independently...

Cancer Medicine

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The American Journal of Surgical Pathology