The myeloid sarcoma treated by Venetoclax with hypomethylating agent followed by stem cell transplantation: rare case report.

BACKGROUND: Myeloid sarcoma (MS) is a very rare condition, develops both in patients with other hematological neoplasms, and as isolated tumor. MS of the gynecologic tract is extremely rare. An available literature data about diagnosis and management of MS is summarized in the article. The role of chemotherapy, radiation therapy, surgery and bone marrow transplantation in the treatment is discussed. Polychemotherapy and allogeneic bone marrow transplantation were suggested to be the optimal treatment strategy of MS of the gynecological tract. The use of new targeted agents results in promising clinical data. CASE PRESENTATION: We are presenting a rare clinical case of a MS of the uterine cervix with concomitant bone marrow involvement and describe all the peculiarities of the clinical course, diagnosis, and treatment. The patient received chemotherapy followed by allogeneic bone marrow transplantation. The pre-transplant therapy allowed us to perform allogeneic bone marrow transplantation with the deepest response possible: complete PET-negative and MRD-negative remission of the disease. CONCLUSIONS: MS remains a subject of discussion regarding its diagnostic and therapeutic aspects. The use of novel targeting agents can be perspective option for patient with extramedullary disease.

Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure.

OBJECTIVES: To the best of our knowledge, data from Gemtuzumab ozogamicin in Acute Myeloid Leukemia (AML) patients with failure of organ functions and poor performance status are extremely lacking. Moreover, the fast recovery from organ failure, after Gemtuzumab ozogamicin administration, has never been reported. This study aimed to demonstrate the efficacy and rapid response of Gemtuzumab ozogamicin in refractory acute myeloid leukemia (AML) patients with pulmonary and kidney failure and poor performance status. Three refractory AML patients, with organ dysfunction, are described. One patient was pre-treated with intensive chemotherapy, and two other patients progressed during Azacitidine treatment. Two patients had respiratory failure grade 2 and one patient suffered from acute kidney insufficiency. Two patients were highly febrile with an elevated С-Reactive Protein (CRP) level. The WHO performance status of three was measured in all patients. Gemtuzumab ozogamicin administration was performed in three patients, followed by a further switch to Gemtuzumab ozogamicin + Azacitidine or "7+3" treatment. RESULTS: Gemtuzumab ozogamicin administration resulted in abrupt fever cessation in two febrile patients simultaneously with a rapid decrease in CRP level and fast resolution of respiratory failure. Recovery of kidney function was noticed rapidly in patients with renal insufficiency. The WHO performance status was elevated in all three patients. No adverse grade II-III effects were noticed. Further treatment made two patients eligible for intensive chemotherapy, one patient underwent allogeneic stem cell transplantation, and the patient with kidney failure obtained complete remission. CONCLUSIONS: Gemtuzumab ozogamicin therapy appeared to be safe and highly efficacious in relapsed/refractory AML patients with organ dysfunction, like pulmonary or renal failure and poor performance status, and may contribute to rapid recovery from organ failures.

Metal-binding properties and structural characterization of a self-assembled coiled coil: formation of a polynuclear Cd-thiolate cluster.

This paper describes the design, characterization, and metal-binding properties of a 32-residue polypeptide called AQ-C16C19. The sequence of this peptide is composed of four repeats of the seven residue sequence Ile-Ala-Ala-Leu-Glu-Gln-Lys but with a Cys-X-X-Cys metal-binding motif substituted at positions 16-19. Size exclusion chromatography with multiangle light scattering detection (SEC-MALS) and circular dichroism (CD) spectroscopy studies showed that the apo peptide exhibits a pH-dependent oligomerization state in which a three-stranded α-helical coiled coil is dominant between pH5.4 and 8.5. The Cd(2+)-binding properties of the AQ-C16C19 peptide were studied by ultraviolet-visible spectroscopy (UV-vis), electrospray ionization mass spectrometry (ESI MS), and (113)Cd NMR techniques. The holoprotein was found to contain a polynuclear cadmium-thiolate center formed within the hydrophobic core of the triple-stranded α-helical coiled-coil structure. The X-ray crystal structure of the Cd-loaded peptide, resolved at 1.85Å resolution, revealed an adamantane-like configuration of the polynuclear metal center consisting of four cadmium ions, six thiolate sulfur ligands from cysteine residues and four oxygen-donor ligands. Three of these are from glutamic acid residues and one is from an exogenous water molecule. Thus, each cadmium ion is coordinated in a distorted tetrahedral S(3)O geometry. The metal cluster was found to form cooperatively at pH5.4 but in a stepwise fashion at pH>7. The results demonstrate that synthetic coiled-coils can be designed to incorporate multinuclear metal clusters, a proof-of-concept for their potential use in developing synthetic metalloenzymes and multi-electron redox agents.

Nanometer to millimeter scale peptide-porphyrin materials.

AQ-Pal14 is a 30-residue polypeptide that was designed to form an α-helical coiled coil that contains a metal-binding 4-pyridylalanine residue on its solvent-exposed surface. However, characterization of this peptide shows that it exists as a three-stranded coiled coil, not a two-stranded one as predicted from its design. Reaction with cobalt(III) protoporphyrin IX (Co-PPIX) produces a six-coordinate Co-PPIX(AQ-Pal14)(2) species that creates two coiled-coil oligomerization domains coordinated to opposite faces of the porphyrin ring. It is found that this species undergoes a buffer-dependent self-assembly process: nanometer-scale globular materials were formed when these components were reacted in unbuffered H(2)O, while millimeter-scale, rod-like materials were prepared when the reaction was performed in phosphate buffer (20 mM, pH 7). It is suggested that assembly of the globular material is dictated by the conformational properties of the coiled-coil forming AQ-Pal14 peptide, whereas that of the rod-like material involves interactions between Co-PPIX and phosphate ion.