Clinical and immunological features in ACKR1/DARC-associated neutropenia.

ACKR1/DARC-associated neutropenia (NP; ADAN; Online Mendelian Inheritance in Man 611862), caused by a variation in the ACKR1/DARC gene (rs2814778), is common in persons of African or Middle Eastern descent. In a cohort of 66 genetically confirmed subjects with ADAN, we show that absolute neutrophil counts (ANCs) may occasionally be lower than previously recognized (0.1 × 109-0.

Characterization of therapy-related acute myeloid leukemia: increasing incidence and prognostic implications.

Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates are lacking. In this study, we characterized, defined the incidence over time and studied prognostic implications in all t-AML patients diagnosed in Sweden between 1997 and 2015. Data were retrieved from nationwide population-based registries.

A risk score based on real-world data to predict early death in acute promyelocytic leukemia.

With increasingly effective treatments, early death (ED) has become the predominant reason for therapeutic failure in patients with acute promyelocytic leukemia (APL). To better prevent ED, patients with high-risk of ED must be identified. Our aim was to develop a score that predicts the risk of ED in a real-life setting.

Is there an impact of measurable residual disease as assessed by multiparameter flow cytometry on survival of AML patients treated in clinical practice? A population-based study.

The Swedish national guidelines for treatment of acute myeloid leukemia (AML) recommend analysis of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in bone marrow in the routine clinical setting. The Swedish AML registry contains such MRD data in AML patients diagnosed 2011-2019. Of 327 patients with AML (non-APL) with MRD-results reported in complete remission after two courses of intensive chemotherapy 229 were MRD-negative (70%), as defined by <0.

Clinical and genomic characterization of patients diagnosed with the provisional entity acute myeloid leukemia with BCR-ABL1, a Swedish population-based study.

Acute myeloid leukemia (AML) with t(9;22)(q34;q11), also known as AML with BCR-ABL1, is a rare, provisional entity in the WHO 2016 classification and is considered a high-risk disease according to the European LeukemiaNet 2017 risk stratification. We here present a retrospective, population-based study of this disease entity from the Swedish Acute Leukemia Registry. By strict clinical inclusion criteria we aimed to identify genetic markers further distinguishing AML with t(9;22) as a separate entity.

AML displays increased CTCF occupancy associated with aberrant gene expression and transcription factor binding.

CCTC-binding factor (CTCF) is a key regulator of gene expression through organization of the chromatin structure. Still, it is unclear how CTCF binding is perturbed in leukemia or in cancer in general. We studied CTCF binding by chromatin immunoprecipitation sequencing in cells from patients with acute myeloid leukemia (AML) and in normal bone marrow (NBM) in the context of gene expression, DNA methylation, and azacitidine exposure.

The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting.

In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect of age and sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data on FLT3-ITD and NPM1 mutations dating to 2007, and 1570 adult patients younger than 75 years, excluding acute promyelocytic leukemia, had molecular results reported. Females more often had FLT3ITD and/or NPM1mut (FLT3ITD: female, 29%; male, 22% [P = .

Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study.

Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018.

Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry.

Objectives And Methods: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry.

Results: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies.

Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes.

The extent and role of aberrant DNA methylation in promoter CpG islands (CGIs) have been extensively studied in leukemia and other malignancies. Still, CGIs represent only a small fraction of the methylome. We aimed to characterize genome-wide differential methylation of cytogenetically normal AML (CN-AML) cells compared with normal CD34(+) bone marrow cells using the Illumina 450K methylation array.

microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia.

A commonly deleted region in chronic lymphocytic leukemia (CLL) is the 11q22-23 region, which encompasses the ATM gene. Evidence suggests that tumor suppressor genes other than ATM are likely to be involved in CLL with del(11q). A microRNA (miR) cluster including the miR-34b and miR-34c genes is located, among other genes, within the commonly deleted region (CDR) at 11q.

A combination regimen of bortezomib, cyclophosphamide and betamethasone gives quicker, better and more durable response than VAD/CyBet regimens: results from a Swedish retrospective analysis.

Background: Induction therapy for multiple myeloma (MM) and remission status before high-dose treatment (HDT) have been shown to be prognostic factors for survival outcome, although the optimal induction therapy is yet to be defined.

Methods: We conducted a retrospective analysis of the impact of induction therapy on survival outcome before and after HDT in MM patients. The study included 236 consecutive patients who underwent HDT.

Epigenetics in myeloid malignancies.

Myeloid hematological malignancies are among the epigenetically best characterized neoplasms. The comparatively low number of recurring balanced and unbalanced chromosomal abnormalities as well as common genetic mutations has enabled scientists to relate epigenetic states to these. The ease of accessing malignant cells through bone marrow aspiration has certainly contributed to the fast expansion of knowledge.

Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks.

Cytogenetically normal acute myeloid leukemia (CN-AML) compose between 40% and 50% of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group, molecular aberrations, such as FLT3-ITD, NPM1, and CEBPA mutations, recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer, including AML.

APR-246 exhibits anti-leukemic activity and synergism with conventional chemotherapeutic drugs in acute myeloid leukemia cells.

Background: APR-246 belongs to a new generation of the compounds that restore normal p53 function in cells with mutated or wild type p53. The purpose of this study was to examine the effects of APR-246 alone and in combination with other drugs in acute myeloid leukemia (AML) cells.

Methods: Primary leukemic cells from patients with AML and AML cell lines were studied with respect to cytotoxic and apoptotic effects and mechanism of action of APR-246, alone and in combination with Ara-C, daunorubicin and fludarabine.

Single nucleotide polymorphism genomic arrays analysis of t(8;21) acute myeloid leukemia cells.

Translocation of chromosomes 8 and 21, t(8;21), resulting in the AML1-ETO fusion gene, is associated with acute myeloid leukemia. We searched for additional genomic abnormalities in this acute myeloid leukemia subtype by performing single nucleotide polymorphism genomic arrays (SNP-chip) analysis on 48 newly diagnosed cases. Thirty-two patients (67%) had a normal genome by SNP-chip analysis (Group A), and 16 patients (33%) had one or more genomic abnormalities including copy number changes or copy number neutral loss of heterozygosity (Group B).

Low p14ARF expression in de novo acute myeloid leukemia with normal karyotype is associated with poor survival.

The p14ARF protein activates the p53 tumor suppressor by binding to and inhibiting its negative regulator HDM-2. We have studied the prognostic impact of p14ARF in acute myeloid leukemia (AML). Leukemic cells from 57 adult patients with normal karyotype de novo AML were analyzed for p14ARF mRNA expression level using real-time polymerase chain reaction (RT-PCR).