Here we describe the major genetic and genomic aberrations found in myeloid malignancies and how those markers are used in patients' diagnosis, prognosis, and targeted treatment. In Bosnia and Herzegovina, cytogenetic and molecular diagnostics for myeloid malignancies have been established and continually improved since 2005. We report the current state of available diagnostic tools for myeloid malignancies in Bosnia and Herzegovina. Myeloid malignancies are a heterogeneous group of clonal blood diseases characterized by defects in hematopoietic stem cells and myeloid progenitors that lead to abnormal proliferation, differentiation, localization, and self-renewal. Most common myeloid malignancies include myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Molecular diagnostics of myeloid malignancies have significantly expanded in the last decade with new genetic and genomic markers for diagnosis, prognosis, and treatment. CONCLUSION: In the last decade, several new genomic markers important for patient diagnosis, prognosis, and therapy have been discovered that need to be implemented in routine molecular diagnostics not only in developed nations but also in developing nations such as Bosnia and Herzegovina.

• Klíčová slova
• Acute Myeloid Leukemia, Molecular Diagnostics, Myelodysplastic Syndrome, Myeloid Neoplasms, Myeloproliferative Neoplasms,
• MeSH
• akutní myeloidní leukemie * diagnóza   genetika   MeSH
• lidé MeSH
• myelodysplastické syndromy * diagnóza   genetika   MeSH
• myeloproliferativní poruchy * diagnóza   genetika   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Bosna a Hercegovina MeSH

Continual progress of knowleges in hematopathology and genetics of hematologic tumors requires actualisation of widely accepted and presently used WHO classification of myeloid neoplasms published 8 years ago. However, the basic principles of this classification remain unchanged, therefore the authors of new WHO classification mention the "revision" of previous and not the introduction o new classification. The aim of this paper is to outline the most important changes of myeloid neoplasm diagnostics to pathologists, hematologists and other clinicians in Czech Republic and Slovakia. This review is based on several papers recently published by opinionleaders in this field.

• Klíčová slova
• WHO classification - myeloid neoplasms - diagnostic criteria.,
• MeSH
• hematologické nádory * diagnóza   MeSH
• lidé MeSH
• myeloproliferativní poruchy * diagnóza   MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

Myeloid/lymphoid neoplasms with eosinophilia (M/LN-eo) and tyrosine kinase (TK) gene fusions are a rare group of haematopoietic neoplasms with a broad range of clinical and morphological presentations. Paediatric cases have increasingly been recognised. Importantly, not all appear as a chronic myeloid neoplasm and eosinophilia is not always present. In addition, standard cytogenetic and molecular methods may not be sufficient to diagnose M/LN-eo due to cytogenetically cryptic aberrations. Therefore, additional evaluation with fluorescence in-situ hybridisation and other molecular genetic techniques (array-based comparative genomic hybridisation, RNA sequencing) are recommended for the identification of specific TK gene fusions. M/LN-eo with JAK2 and FLT3-rearrangements and ETV6::ABL1 fusion were recently added as a formal member to this category in the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO-HAEM5). In addition, other less common defined genetic alterations involving TK genes have been described. This study is an update on M/LN-eo with TK gene fusions with focus on novel entities, as illustrated by cases submitted to the Bone Marrow Workshop, organised by the European Bone Marrow Working Group (EBMWG) within the frame of the 21st European Association for Haematopathology congress (EAHP-SH) in Florence 2022. A literature review was performed including paediatric cases of M/LN-eo with TK gene fusions.

• Klíčová slova
• European Bone Marrow Working Group (EBMWG), bone marrow biopsy, myeloid/lymphoid neoplasms with eosinophilia, paediatric, tyrosine kinase gene fusion,
• MeSH
• dítě MeSH
• eozinofilie * genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• hematologické nádory * patologie   MeSH
• kostní dřeň patologie   MeSH
• lidé MeSH
• lymfom * patologie   MeSH
• myeloproliferativní poruchy * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH

In the present study we compared outcomes of patients with myeloid neoplasms undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with melphalan (FM140) or 3-day busulfan (FB3). The FM140 and FB3 combinations were administered to 21 and 27 patients, respectively. Efforts for early reduction (from day +30 to 60) and discontinuation (until day +100 to 130) of prophylactic immunosuppression were a component of the post-transplant approach. Following FB3 patients suffered from more severe stomatitis (P = 0.013). In contrast, other manifestations of regimen-related toxicity were more frequent in the FM140 group (P = 0.048). There were no statistically significant differences in the development of graft-versus-host disease, non-relapse mortality, post-transplant remission rate, or relapse incidence. Two-year disease-free survival rates were comparable in the two cohorts (66 vs. 55 %; P = 0.751), and so were the overall survival rates (64 vs. 62 %; P = 0.715). The outcomes of allografted patients with myeloid neoplasms were comparable after the FM140 and FB3 regimens. Relatively high therapeutic response in both groups may have been influenced by early reduction and discontinuation of prophylactic immunosuppression followed by effective immunological control of the malignant clone.

• MeSH
• dospělí MeSH
• homologní transplantace MeSH
• lidé středního věku MeSH
• lidé MeSH
• melfalan aplikace a dávkování   MeSH
• mladý dospělý MeSH
• myelodysplastické syndromy terapie   MeSH
• myeloidní leukemie terapie   MeSH
• nemoc štěpu proti hostiteli diagnóza   etiologie   prevence a kontrola   MeSH
• příprava pacienta k transplantaci * metody   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• vidarabin aplikace a dávkování   analogy a deriváty   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• fludarabine MeSH Prohlížeč
• melfalan MeSH
• vidarabin MeSH

Myeloproliferative neoplasms (MPN) are genetically very complex and heterogeneous diseases in which the acquisition of a somatic driver mutation triggers three main myeloid cytokine receptors, and phenotypically expresses as polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The course of the diseases may be influenced by germline predispositions, modifying mutations, their order of acquisition and environmental factors such as aging and inflammation. Deciphering these contributory elements, their mutual interrelationships, and their contribution to MPN pathogenesis brings important insights into the diseases. Animal models (mainly mouse and zebrafish) have already significantly contributed to understanding the role of several acquired and germline mutations in MPN oncogenic signaling. Novel technologies such as induced pluripotent stem cells (iPSCs) and precise genome editing (using CRISPR/Cas9) contribute to the emerging understanding of MPN pathogenesis and clonal architecture, and form a convenient platform for evaluating drug efficacy. In this overview, the genetic landscape of MPN is briefly described, with an attempt to cover the main discoveries of the last 15 years. Mouse and zebrafish models of the driver mutations are discussed and followed by a review of recent progress in modeling MPN with patient-derived iPSCs and CRISPR/Cas9 gene editing.

• Klíčová slova
• CALR, JAK2, MPL, MPN (myeloproliferative neoplasms), iPSCs, mice, thrombosis, zebrafish,
• MeSH
• dánio pruhované MeSH
• esenciální trombocytemie genetika   MeSH
• fenotyp MeSH
• indukované pluripotentní kmenové buňky metabolismus   MeSH
• Janus kinasa 2 genetika   MeSH
• kalretikulin genetika   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mutace MeSH
• myeloproliferativní poruchy genetika   patofyziologie   MeSH
• myši MeSH
• nádory genetika   MeSH
• polycythaemia vera genetika   MeSH
• primární myelofibróza genetika   MeSH
• receptory thrombopoetinu genetika   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• Janus kinasa 2 MeSH
• kalretikulin MeSH
• receptory thrombopoetinu MeSH

Cytogenomic investigations of haematological neoplasms, including chromosome banding analysis, fluorescence in situ hybridisation (FISH) and microarray analyses have become increasingly important in the clinical management of patients with haematological neoplasms. The widespread implementation of these techniques in genetic diagnostics has highlighted the need for guidance on the essential criteria to follow when providing cytogenomic testing, regardless of choice of methodology. These recommendations provide an updated, practical and easily available document that will assist laboratories in the choice of testing and methodology enabling them to operate within acceptable standards and maintain a quality service.

• MeSH
• akutní myeloidní leukemie genetika   MeSH
• chronická myeloidní leukemie MeSH
• hematologické nádory genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• lymfom genetika   MeSH
• mikročipová analýza MeSH
• mnohočetný myelom genetika   MeSH
• myelodysplastické syndromy MeSH
• pruhování chromozomů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIM: The aim of this work was to retrospectively analyze patients with Philadelphia-negative myeloproliferative neoplasms through evaluation of frequency and characteristics of second malignancies (other than acute leukaemia and myelodysplastic syndrome). PATIENTS AND METHODS: Records of 172 patients were reviewed; an analysis was performed on data from 66 patients treated with hydroxyurea, 105 patients treated with other cytoreductive therapy, and 25 patients without treatment. RESULTS: A higher occurrence of second malignancies was found in the group treated with hydroxyurea (7.6%; other cytoreduction: 1.2%; without therapy: 0). After a median follow-up of 89 months in the hydroxyurea group, 13 patients developed second cancer during hydroxyurea therapy, located on the skin (68.75%) and other sites (31.25%). CONCLUSION: The incidence of second malignancies during hydroxyurea therapy in our cohort patient was significantly higher than the incidence of malignancies in the Czech population of corresponding age.

• Klíčová slova
• Second malignancies, hydroxyurea, myeloproliferative neoplasm, skin cancer,
• MeSH
• antitumorózní látky terapeutické užití   MeSH
• hydroxymočovina terapeutické užití   MeSH
• incidence MeSH
• leukemie myeloidní chronická atypická BCR-ABL-negativní farmakoterapie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• sekundární malignity epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• hydroxymočovina MeSH

INTRODUCTION: To date, no chemoresistance predictors are included in acute myeloid leukaemia (AML) prognostic scoring systems to distinguish responding and refractory AML patients prior to chemotherapy. ABC transporters have been described as altering AML chemosensitivity; however, a relevant study investigating their role at various molecular levels was lacking. METHODS: Gene expression, genetic variants, methylation and activity of ABCA2, ABCA5, ABCB1, ABCB6, ABCC1, ABCC3 and ABCG2 were analysed in AML blasts and healthy myeloblasts. Differences between responding and refractory AML in a cohort of 113 patients treated with 3 + 7 induction therapy were explored. RESULTS: ABCC3 variant rs2301837 (p = 0.049), ABCG2 variant rs11736552 (p = 0.044), higher ABCA2 (p = 0.021), ABCC1 (p = 0.017), and ABCG2 expression (p = 0.023) and a higher number of concurrently overexpressed transporters (p = 0.002) were predictive of treatment failure by multivariate analysis. Expression of ABCA5 (p = 0.003), ABCB6 (p = 0.001) and ABCC3 (p < 0.0001) increased significantly after chemotherapy. Higher ABCG2 promoter methylation correlated with lower ABCG2 expression (p = 0.0001). ABCC1 was identified as the most active transporter in AML blasts by functional analysis. CONCLUSIONS: ABC transporters, especially ABCC1 seem to contribute substantially to AML chemoresistance. A detailed understanding of chemoresistance mechanisms and the clinical implications of chemosensitivity predictors may lead to alternative therapeutic approaches for AML patients with unveiled chemoresistance signatures.

• Klíčová slova
• ABC transporter, Acute myeloid leukemia, Anthracycline, Chemoresistance,
• MeSH
• ABC transportéry * metabolismus   MeSH
• akutní myeloidní leukemie * farmakoterapie   genetika   MeSH
• chemorezistence genetika   MeSH
• lidé MeSH
• terapie neúspěšná MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportéry * MeSH

Secondary acute myeloid leukemia (sAML) may arise from the previous clonal disorder of hematopoiesis, usually from myelodysplastic syndrome (MDS) or from chronic myeloproliferative neoplasia (cMPN) or after exposure to a leukemogenic agent (previous chemotherapy or radiotherapy, some immunosuppressive drugs or environmental leukemogenic agents). Secondary origin of AML is associated with unfavorable prognosis and it is not considered to be conventionally curable (with the exception of secondary acute promyelocytic leukemia). The presented study is a retrospective analysis of patients diagnosed and treated at the Department of Hemato-Oncology, University Hospital Olomouc in 1996-2008. Over that period of time, a total 574 patients with AML were diagnosed. Of those, 430 patients were diagnosed as having primary AML; in 86 patients, sAML transformed from myelodysplastic syndrome and 58 patients were followed or treated for various malignancies or were treated with potentially leukemogenic agents because of non-malignant disorders. Patients with secondary AML are older and less commonly treated with curative intention than those with primary AML. According to cytogenetic findings, their prognosis is often worse. Complete hematologic remission is achieved with a low probability, relapse of the disease occurs frequently and overall survival is worse in almost all prognostic subgroups. With the exception of secondary acute promyelocytic leukemia, the prognosis of which does not differ from very good prognosis of the primary forms, secondary AML is not considered a conventionally curable disease.

• MeSH
• akutní myeloidní leukemie etiologie   terapie   MeSH
• chronická nemoc MeSH
• dospělí MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru etiologie   terapie   MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• myelodysplastické syndromy komplikace   terapie   MeSH
• myeloproliferativní poruchy komplikace   terapie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• sekundární malignity etiologie   terapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0-6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1-5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.

• Klíčová slova
• CHIP and FCR, CLL, t-MN,
• MeSH
• chronická lymfatická leukemie * farmakoterapie   genetika   patologie   MeSH
• klonální hematopoéza genetika   MeSH
• lidé MeSH
• mutace MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• rizikové faktory MeSH
• sekundární malignity * etiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH