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Cammenga, Jörg
Publications (6 of 6) Show all publications
Baliakas, P., Tesi, B., Wartiovaara-Kautto, U., Stray-Pedersen, A., Friis, L. S., Dybedal, I., . . . Andersen, M. K. (2019). Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up. HEMASPHERE, 3(6), Article ID UNSP e321.
Open this publication in new window or tab >>Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up
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2019 (English)In: HEMASPHERE, Vol. 3, no 6, article id UNSP e321Article in journal (Refereed) Published
Abstract [en]

Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-163763 (URN)10.1097/HS9.0000000000000321 (DOI)000508564100020 ()31976490 (PubMedID)
Note

Funding Agencies|Nordic Cancer Union (NCU)

Available from: 2020-02-19 Created: 2020-02-19 Last updated: 2020-02-19
Eriksson, M., Peña-Martínez, P., Ramakrishnan, R., Chapellier, M., Högberg, C., Glowacki, G., . . . Järås, M. (2017). Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NF?B-dependent differentiation of AML cells. Blood advances, 1(23), 2046-2057
Open this publication in new window or tab >>Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NF?B-dependent differentiation of AML cells
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2017 (English)In: Blood advances, ISSN 2473-9529, Vol. 1, no 23, p. 2046-2057Article in journal (Refereed) Published
Abstract [en]

Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driven human AML resulted in induction of apoptosis by p38 MAPK-dependent activation of Caspase 3 and myeloid differentiation in a NF?B-dependent manner. By using murineTrp53 -/- MLL-AF9AML cells, we demonstrate that p53 is dispensable for Pam3CSK4-induced apoptosis and differentiation. Moreover, murineAML1-ETO9a-driven AML cells also were forced into apoptosis and differentiation on TLR1/TLR2 activation, demonstrating that the antileukemic effects observed were not confined toMLL-rearranged AML. We further evaluated whether Pam3CSK4 would exhibit selective antileukemic effects. Ex vivo Pam3CSK4 treatment inhibited murine and human leukemia-initiating cells, whereas murine normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected. Consistent with these findings, primary human AML cells across several genetic subtypes of AML were more vulnerable for TLR1/TLR2 activation relative to normal human HSPCs. In theMLL-AF9AML mouse model, treatment with Pam3CSK4 provided proof of concept for in vivo therapeutic efficacy. Our results demonstrate that TLR1 and TLR2 are upregulated on primitive AML cells and that agonistic targeting of TLR1/TLR2 forces AML cells into apoptosis by p38 MAPK-dependent activation of Caspase 3, and differentiation by activating NF?B, thus revealing a new putative strategy for therapeutically targeting AML cells.

Place, publisher, year, edition, pages
American Society of Hematology, 2017
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-146332 (URN)10.1182/bloodadvances.2017006148 (DOI)000413645600008 ()29296851 (PubMedID)
Available from: 2018-04-07 Created: 2018-04-07 Last updated: 2020-01-18
Baudet, A., Ek, F., Davidsson, J., Soneji, S., Olsson, R., Magnusson, M., . . . Juliusson, G. (2016). Small molecule screen identifies differentiation-promoting compounds targeting genetically diverse acute myeloid leukaemia [Letter to the editor]. British Journal of Haematology, 175(2), 342-346
Open this publication in new window or tab >>Small molecule screen identifies differentiation-promoting compounds targeting genetically diverse acute myeloid leukaemia
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2016 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 175, no 2, p. 342-346Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2016
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-126592 (URN)10.1111/bjh.13851 (DOI)000385763400020 ()26567888 (PubMedID)2-s2.0-84947739123 (Scopus ID)
Available from: 2016-03-30 Created: 2016-03-30 Last updated: 2018-03-19Bibliographically approved
Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Doehner, H., . . . Zieger, B. (2016). The European Hematology Association Roadmap for European Hematology Research: a consensus document. Haematologica, 101(2), 115-208
Open this publication in new window or tab >>The European Hematology Association Roadmap for European Hematology Research: a consensus document
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 2, p. 115-208Article in journal (Refereed) Published
Abstract [en]

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

Place, publisher, year, edition, pages
Pavia, Italy: Fondazione Ferrata Storti, 2016
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-143791 (URN)10.3324/haematol.2015.136739 (DOI)000379156300012 ()26819058 (PubMedID)2-s2.0-84981361090 (Scopus ID)
Note

Funding Agencies|Cancer Research UK [12765]; Medical Research Council [MR/L022982/1, MC_UU_12009/8, MC_PC_12009, MC_U137981013]; British Heart Foundation [FS/09/039/27788]

Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2018-01-09Bibliographically approved
Velasco-Hernandez, T., Tornero, D. & Cammenga, J. (2015). Loss of HIF-1 alpha accelerates murine FLT-3(ITD)-induced myeloproliferative neoplasia. Leukemia, 29(12), 2366-2374
Open this publication in new window or tab >>Loss of HIF-1 alpha accelerates murine FLT-3(ITD)-induced myeloproliferative neoplasia
2015 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, no 12, p. 2366-2374Article in journal (Refereed) Published
Abstract [en]

Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha) has a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs), as well as leukemia-initiating cells (LICs) of acute myeloid leukemia and chronic myeloid leukemia. We have investigated the effect of HIF-1 alpha loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1 alpha leads to an enhanced MPN phenotype reflected by an increased number of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1 alpha loss is cell intrinsic as shown by transplantation into recipient mice. HSC loss and organ-specific changes in the number and percentage of long-term HSCs were the most pronounced effects on a cellular level after HIF-1 alpha deletion. Furthermore, we found a metabolic hyperactivation of malignant cells in the spleen upon loss of HIF-1 alpha. Some of our findings are in contrary to what has been previously described for the role of HIF-1 alpha in other myeloid hematologic malignancies and question the potential of HIF-1 alpha as a therapeutic target.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2015
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-123766 (URN)10.1038/leu.2015.156 (DOI)000366393900011 ()26104662 (PubMedID)
Note

Funding Agencies|Barncancerfonden; Cancerfonden; SSF through the Hemato-Linne and StemTherapy consortium (Sweden); Barncancerfonden (Sweden)

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-11-30
Lübking, A., Vosberg, S., Konstandin, N., Dufour, A., Graf, A., Krebs, S., . . . Cammenga, J. (2015). Young woman with mild bone marrow dysplasia, GATA2 and ASXL1 mutation treated with allogeneic hematopoietic stem cell transplantation. Leukemia Research Reports, 4(2), 72-75
Open this publication in new window or tab >>Young woman with mild bone marrow dysplasia, GATA2 and ASXL1 mutation treated with allogeneic hematopoietic stem cell transplantation
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2015 (English)In: Leukemia Research Reports, ISSN 2213-0489, Vol. 4, no 2, p. 72-75Article in journal (Refereed) Published
Abstract [en]

Heterozygous mutations in GATA2 underlie different syndromes, previously described as monocytopenia and mycobacterial avium complex infection (MonoMAC); dendritic cell, monocytes, B- and NK lymphocytes deficiency (DCML); lymphedema, deafness and myelodysplasia (Emberger syndrome) and familiar myelodysplastic syndrome/acute myeloid leukemia (MDS / AML). Onset and severity of clinical symptoms vary and preceding cytopenias are not always present. We describe a case of symptomatic DCML deficiency and rather discrete bone marrow findings due to GATA2 mutation. Exome sequencing revealed a somatic ASXL1 mutation and the patient underwent allogeneic stem cell transplantation successfully. © 2015.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
GATA2 mutation; Myelodysplastic syndrome; ASXL1 mutation; Allogeneic hematopoietic stem cell transplantation
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-126593 (URN)10.1016/j.lrr.2015.10.001 (DOI)26716079 (PubMedID)2-s2.0-84945266216 (Scopus ID)
Available from: 2016-03-30 Created: 2016-03-30 Last updated: 2016-04-20Bibliographically approved
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