Outcomes for patients with chronic lymphocytic leukemia and acute leukemia or myelodysplastic syndrome

Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in chronic lymphocytic leukemia (CLL). We retrospectively identified 95 patients with CLL, also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2 (0-9) and 1 (0-8), respectively; the most common regimen was purine analog combined with alkylating agent±CD20 monoclonal antibody. Twelve cases had no prior CLL treatment. Among 38 cases with AL, 33 had acute myelogenous leukemia (AML), 3 had acute lymphoid leukemia (ALL; 1 Philadelphia chromosome positive), 1 had biphenotypic and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, and intermediate risk in 7 patients. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all International Prognostic Scoring System (IPSS) were represented; karyotype was unfavorable in 36, intermediate in 6 and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher risk IPSS, poor-risk karyotype and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were very poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed

Histone acetyltransferase inhibitors and preclinical studies

Background: Drugs able to regulate the histone modifier enzymes are very promising tools for the treatment of several diseases, such as cancer. Histone acetyltransferase (HAT) inhibitors are compounds able to inhibit the catalytic activity of HATS reported to be active in cancer, or in several other diseases, such as Alzheimer (AD), diabetes and hyperlipidaemia. Objectives: Here we review the status and the rationale for the use of HAT inhibitors in the treatment of various diseases. Methods: Patents have been found on the espacenet database; the clinical trials have been reported as in the clinical-trial.gov website. Results and conclusion: Despite the fact that other drugs able to regulate the histone modifier enzymes (such as histone deacetylase inhibitors) have been already approved for the treatment of cancer, HAT inhibitors seem promising for the treatment of human diseases such as AD and diabetes, although side effects and toxicity need to be investigated

A glance on Immunogenetics Laboratory: from the origins to the future

Histocompatibility and Immunogenetics (H&I) laboratories have currently a significant relevance in clinical and research medical fields. The purpose of this review is to investigate their role through an excursus between bioethics, histocompatibility history and laboratory organization. The histocompatibility laboratories play an essential role in the transplantation process, and, through their molecular techniques, they can affect clinical decisions in a remarkable way. Half a century has passed from the first paper, published in 1958, to the modern deep sequencing techniques; in these years through specific guidelines and international standards drafted by 2 specific bodies (ASHI and EFI), H&I laboratories are subjected to continuous controls by inspection authorities formed by professionals in the Immunogenetics field. For their functioning, H&I laboratories require: a structure and devices, a dedicated room and a clear path to samples workflow. In these laboratories, the personnel must be specialized even just in a single precise assignment, and every member is assigned to a role according to the experience matured over the years. In these laboratories, the role of Director/Co-Director or Technical Supervisor is usually assigned to a staff member with a minimum of 4 years of experience in Immunogenetics or transplantation fields, following the EFI/ASHI Standards. Bioethics is another important aspect because, in the last few years, there has been a major change in legal regulations on informed consent. The advent of digitization has pushed many laws on personal and genetic data treatment to be adapted to most modern guidelines, although they may differ according to the countries in Europe and USA. In the last years, the H&I laboratories turned as great resources with many clinical features and nowadays they may lead an important transformation in research and clinical fields

HDAC Inhibitors Repress BARD1 Isoform Expression in Acute Myeloid Leukemia Cells via Activation of miR-19a and/or b.

Over the past years BARD1 (BRCA1-associated RING domain 1) has been considered as both a BRCA1 (BReast Cancer susceptibility gene 1, early onset) interactor and tumor suppressor gene mutated in breast and ovarian cancers. Despite its role as a stable heterodimer with BRCA1, increasing evidence indicates that BARD1 also has BRCA1-independent oncogenic functions. Here, we investigate BARD1 expression and function in human acute myeloid leukemias and its modulation by epigenetic mechanism(s) and microRNAs. We show that the HDACi (histone deacetylase inhibitor) Vorinostat reduces BARD1 mRNA levels by increasing miR-19a and miR-19b expression levels. Moreover, we identify a specific BARD1 isoform, which might act as tumor diagnostic and prognostic markers