Utility of Targeted Sequencing Compared to FISH for Detection of Chronic Lymphocytic Leukemia Copy Number Alterations.

Chronic lymphocytic leukemia (CLL) is characterized by multiple copy number alterations (CNAs) and somatic mutations that are central to disease prognosis, risk stratification, and mechanisms of therapy resistance. Fluorescence in situ hybridization (FISH) panels are widely used in clinical applications as the gold standard for screening prognostic chromosomal abnormalities in CLL. DNA sequencing is an alternative approach to identifying CNAs but is not an established method for clinical CNA screening.

Differential prognosis of single and multiple TP53 abnormalities in high-count MBL and untreated CLL.

TP53 aberrations, including mutations and deletion of 17p13, are important adverse prognostic markers in chronic lymphocytic leukemia (CLL) but are less studied in high count monoclonal B-cell lymphocytosis (HCMBL), an asymptomatic pre-malignant stage of CLL. Here we estimated the prevalence and impact of TP53 aberrations in 1,230 newly diagnosed treatment-naïve individuals (849 CLL, 381 HCMBL). We defined TP53 state as: wild-type (no TP53 mutations and normal 17p), single-hit (del(17p) or one TP53 mutation), or multi-hit (TP53 mutation and del(17p), TP53 mutation and loss of heterozygosity, or multiple TP53 mutations).

Dental Caries Risk Assessment in Children 5 Years Old and under via Machine Learning.

Background: Dental caries is a prevalent, complex, chronic illness that is avoidable. Better dental health outcomes are achieved as a result of accurate and early caries risk prediction in children, which also helps to avoid additional expenses and repercussions. In recent years, artificial intelligence (AI) has been employed in the medical field to aid in the diagnosis and treatment of medical diseases.

Clinical outcomes in patients with chronic lymphocytic leukemia with disease progression on ibrutinib.

Patients with chronic lymphocytic leukemia (CLL) with disease progression on ibrutinib have worse outcomes compared to patients stopping ibrutinib due to toxicity. A better understanding of expected outcomes in these patients is necessary to establish a benchmark for evaluating novel agents currently available and in development. We evaluated outcomes of 144 patients with CLL treated at Mayo Clinic with 2018 iwCLL disease progression on ibrutinib.

CLL update 2022: A continuing evolution in care.

Chronic lymphocytic leukemia (CLL) is diagnosed by the presence of a specific immunophenotype of clonal B cells in the peripheral blood. Prognostic models such as the CLL-International Prognostic Index (CLL-IPI) are now available that evaluate risk and assist in counseling individual patients. High risk CLL is characterized as the presence of del17p13, TP53 mutations and complex karyotype.

Utilizing next-generation sequencing to characterize a case of acute myeloid leukemia with t(4;12)(q12;p13) in the absence of ETV6/CHIC2 and ETV6/PDGFRA gene fusions.

The t(4;12)(q12;p13) has been rarely reported in both myeloid/lymphoid neoplasms with eosinophilia (ETV6/PDGFRA gene fusion) and acute myeloid leukemia (AML) (ETV6/CHIC2 gene fusion). The ability to accurately characterize t(4;12) is critical as myeloid neoplasms with PDGFRA rearrangements may be amenable to tyrosine kinase inhibitor (TKI) therapy. Herein, we describe a 60-year-old male with newly diagnosed AML and t(4;12)(q12;p13) by conventional chromosome studies.

MCIR1: A patient-derived mantle cell lymphoma line for discovering new treatments for ibrutinib resistance.

Background: Despite the unprecedented success of ibrutinib in lymphoma therapy, the development of ibrutinib resistance due to acquired BTK or PLCγ2 mutations has become a new clinical problem. However, not all resistance is mediated by these mutations and these mechanisms are poorly understood due to a lack of study tools that truly recapitulate this clinical scenario.

Methods: We established a novel patient-derived ibrutinib-resistant mantle cell lymphoma (MCL) line named MCIR1.

Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome.

Richter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such as TP53 and NOTCH1 mutations. However, it is unclear what immune microenvironment changes are associated with RS.

The CLL International Prognostic Index predicts outcomes in monoclonal B-cell lymphocytosis and Rai 0 CLL.

The utility of the chronic lymphocytic leukemia-international prognostic index (CLL-IPI) in predicting outcomes of individuals with Rai 0 stage CLL and monoclonal B-cell lymphocytosis (MBL) is unclear. We identified 969 individuals (415 MBL and 554 Rai 0 CLL; median age, 64 years; 65% men) seen at Mayo Clinic between 1 January 2001 and 1 October 2018, and ascertained time to first therapy (TTFT) and overall survival (OS). After a median follow up of 7 years, the risk of disease progression needing therapy was 2.

Disease Flare During Temporary Interruption of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia.

Background: Approximately 25% of patients with chronic lymphocytic leukemia (CLL) experience a flare of disease following ibrutinib discontinuation. A critical question is whether this phenomenon may also occur when ibrutinib is temporarily held. This study aimed to determine the frequency and characteristics of disease flares in this setting and assess risk factors and clinical outcomes.

Clinical characteristics and outcomes of Richter transformation: experience of 204 patients from a single center.

The natural history, prognostication and optimal treatment of Richter transformation developed from chronic lymphocytic leukemia (CLL) are not well defined. We report the clinical characteristics and outcomes of a large series of biopsy-confirmed Richter transformation (diffuse large B-cell lymphoma or high grade B-cell lymphoma, n=204) cases diagnosed from 1993 to 2018. After a median follow up of 67.

Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls.

Background: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass.

Case Report: Fine-needle aspiration showed features suggestive of Warthin tumor.

IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes.

The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH-BCL2 and IGH-BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH-BCL2 and IGH-BCL3 translocation were compared to patients without these abnormalities (non-IGH group).

Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia.

The prognostic role of cytogenetic analysis is well-established in B-cell chronic lymphocytic leukemia (CLL). Approximately 80% of patients have a cytogenetic aberration. Interphase FISH panels have been the gold standard for cytogenetic evaluation, but conventional cytogenetics allows detection of additional abnormalities, including translocations, complex karyotypes and multiple clones.

Analysis of Common Abnormalities Seen in Chronic Lymphocytic Leukemia Using Fluorescence In Situ Hybridization.

Since fluorescence in situ hybridization (FISH) was used to define a prognostic heierarchy for chronic lymphocytic leukemia (CLL) in 2000, the method has been employed widely in cytogenetics laboratories worldwide. This chapter describes techniques and trouble-shooting to maximize the efficiency of microscope slide preparation for FISH analysis in CLL.