Ľuboš Janotka

Germline Jak2-R1063H mutation interferes with normal hematopoietic development and increases risk of thrombosis and leukemic transformation

Veronika Zimolova, Monika Burócziová, Linda Berková, Srdjan Grusanovic et autres

The acquired JAK2-V617F mutation plays a causal role in myeloproliferative neoplasms (MPN). Weakly activating JAK2 germline variants have been associated with MPN risk, but the underlying mechanisms remain unclear. We previously identified the JAK2-R1063H germline variant, which contributes to hereditary MPN and …

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Acquired Resistance to Decitabine Associated with the Deoxycytidine Kinase A180P Mutation: Implications for the Order of Hypomethylating Agents in Myeloid Malignancies Treatment

Kristína Šimoničová, Ľuboš Janotka, Helena Kavcová, Ivana Borovská et autres

The backbone of therapy for elderly patients with myelodysplastic syndromes and acute myeloid leukemia consists of hypomethylating agents 5-aza-2’-deoxycytidine (DAC) and 5-azacytidine (AZA). However, resistance frequently emerges during treatment. To investigate the mechanisms of resistance, we generated DAC-resistant variants of the acute …

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Differential Response to ATR/Chk1 Inhibition in Preleukemia and Transformed Leukemia in an MLL-ENL Model of Leukemogenesis Reflects Enrichment for Myc-Transcriptional Program

Pavla Chaloupková, Ľuboš Janotka, Ján Gurský, Nikola Niederlova et autres

We study a dual role of ATR/Chk1 signaling in preleukemia and fully transformed AML and their vulnerability to specific inhibitors (i). We previously reported oncogene-inducible Mll-ENL mouse model, with AML evolving from preleukemia after a long latency period (Takacova et al, PMID: …

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Resistance of Leukemia Cells to 5-Azacytidine: Different Responses to the Same Induction Protocol

Kristína Šimoničová, Ľuboš Janotka, Helena Kavcová, Zdena Sulová et autres

Three AML cell variants (M/A, M/A* from MOLM-13 and S/A from SKM-1) were established for resistance by the same protocol using 5-azacytidine (AZA) as a selection agent. These AZA-resistant variants differ in their responses to other cytosine nucleoside analogs, including 5-aza-2'-deoxycytidine (DAC), …

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CCDC 2058692: Experimental Crystal Structure Determination

Lukáš Ďurina, Anna Ďurinová, František Trejtnar, Ľuboš Janotka et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Different mechanisms of drug resistance to hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukemia

Kristína Šimoničová, Ľuboš Janotka, Helena Kavcová, Zdena Sulová et autres

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CCDC 2099851: Experimental Crystal Structure Determination

Lukáš Ďurina, Anna Ďurinová, František Trejtnar, Ľuboš Janotka et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

Lukáš Ďurina, Anna Ďurinová, František Trejtnar, Ľuboš Janotka et autres

A new highly diastereoselective synthesis of the polyhydroxylated pyrrolidine alkaloid (±)-codonopsinol B and its N-nor-methyl analogue, starting from achiral materials, is presented. The strategy relies on the trans-stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the syn-selective α-chelation-controlled addition of vinyl-MgBr/CeCl3 to …

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Topic: AS08-Treatment/AS08a-Current treatment options - Hypomethylating agents

Kristína Šimoničová, Ľuboš Janotka, Helena Kavcová, Lucia Messingerová et autres

Changes in Apoptotic Pathways in MOLM-13 Cell Lines after Induction of Resistance to Hypomethylating Agents

Ľuboš Janotka, Lucia Messingerová, Kristína Šimoničová, Helena Kavcová et autres

We established the following two variants of the MOLM-13 human acute myeloid leukemia (AML) cell line: (i) MOLM-13/DAC cells are resistant to 5-aza-2'-deoxycytidine (DAC), and (ii) MOLM-13/AZA are resistant to 5-azacytidine (AZA). Both cell variants were obtained through a six-month selection/adaptation procedure …

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CCDC 1997748: Experimental Crystal Structure Determination

Radka Štadániová, Michal Sahulčík, Jana Doháňošová, Ján Moncóľ et autres

Synthesis of 1,2,3‐Triazoles Bearing a 4‐Hydroxyisoxazolidine Moiety from 4,5‐Unsubstituted 2,3‐Dihydroisoxazoles

Radka Štadániová, Michal Sahulčík, Jana Doháňošová, Ján Moncóľ et autres

A synthetic approach towards new 1,2,3‐triazoles bearing the 3‐hydroxymethylated 4‐hydroxyisoxazolidine moiety has been described. The strategy has relied on dihydroxylation and epoxidation reactions of 4,5‐unsubstituted 2,3‐dihydroisoxazoles, allowing the introduction of the hydroxy group at the isoxazolidine ring in a trans stereoselective manner …

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