Clinical utility of next generation sequencing to detect IGH/IL3 rearrangements [t(5;14)(q31.1;q32.1)] in B-lymphoblastic leukemia/lymphoma.

The t(5;14)(q31.1;q32.1) associated with B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is a rare, recurrent genetic abnormality recognized as a distinct entity by the 2017 World Health Organization (WHO) classification.

Siblings with ETV6/RUNX1-positive B-lymphoblastic leukemia: A single site experience and review of the literature.

Siblings diagnosed with B-lymphoblastic leukemia (B-ALL) that share the same driver abnormality have been rarely described in the literature. Herein, we report three pairs of siblings (one non-identical pair, one maternal half-sibling pair, and one identical pair) all diagnosed with ETV6/RUNX1-positive B-ALL. Considering that ETV6/RUNX1 fusion is thought to represent a prenatal event and necessitates additional genomic alterations to result in leukemia, siblings of patient's with known ETV6/RUNX1-positive B-ALL may be at increased risk of ETV6/RUNX1-positive B-ALL due to common exposures (environmental or infectious) or shared germline polymorphisms.

Characterization of TCF3 rearrangements in pediatric B-lymphoblastic leukemia/lymphoma by mate-pair sequencing (MPseq) identifies complex genomic rearrangements and a novel TCF3/TEF gene fusion.

The TCF3/PBX1 gene fusion is a recurrent genetic abnormality in pediatric B-lymphoblastic leukemia/lymphoma (B-ALL/LBL). While dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) probes can detect TCF3/PBX1 fusions, further characterization of atypical TCF3 FISH patterns as indicated by additional or diminished TCF3 signals is currently limited. Herein we describe the use of a next-generation sequencing assay, mate-pair sequencing (MPseq), to characterize typical and cryptic TCF3/PBX1 fusions and to identify TCF3 translocation partners based on results obtained from our laboratory-developed TCF3/PBX1 D-FISH probe set.

Acute leukemias harboring KMT2A/MLLT10 fusion: a 10-year experience from a single genomics laboratory.

The MLLT10 (formerly AF10) gene is the fourth most common KMT2A fusion partner across all acute leukemias and requires at least 3 breaks to form an in-frame KMT2A/MLLT10 fusion due to the opposite orientation of each gene. A 10-year retrospective review was performed to identify individuals from all age groups that harbor KMT2A/MLLT10 fusion obtained by our KMT2A/MLLT10 dual-color dual-fusion fluorescence in situ hybridization (D-FISH) assay. Of the 60 unique individuals identified, 31 were male and 29 were female (M:F ratio, 1.

KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma: A 10-year review from a single cytogenetic laboratory.

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4-8% of T-ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T-ALL/LBL. A 10-year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T-ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years.

A rapid and reliable chromosome analysis method for products of conception using interphase nuclei.

Background: Karyotype determination has a central role in the genetic workup of pregnancy loss, as aneuploidy (trisomy and monosomy) and polyploidy (triploidy and tetraploidy) are the cause in at least 50% of first trimester, 25% of second trimester, and 11% of third trimester miscarriages. There are several limitations with the current approaches of obtaining a karyotype using traditional cytogenetics, fluorescence in situ hybridization with a limited number of probes, and chromosomal microarray. These include culture failure, incomplete results, lower sensitivity, and longer reporting time.

Subjectivity in chromosome band-level estimation: a multicenter study.

Purpose: Chromosome band level is the primary quality indicator for G-banded metaphase chromosome analysis. Although current professional guidelines address the minimum necessary band level for constitutional studies, there is no study documenting the comparative performance of different band-level estimation methods.

Methods: This study compared 5 band-level estimation methods (Stallard, Vancouver, Welborn, United Kingdom External Quality Assurance Scheme, and Ford) in a multicenter study in which 82 readers from 7 different clinical cytogenetics laboratories evaluated the same 10 karyotypes (5 from amniotic fluid and 5 from peripheral blood) by each method.

Development of five dual-color, double-fusion fluorescence in situ hybridization assays for the detection of common MLL translocation partners.

Chromosomal rearrangements involving the mixed lineage leukemia (MLL) gene at 11q23 are frequent in adult and childhood acute leukemia and have been associated with an unfavorable prognosis. Recent evidence suggests that MLL gene partners may influence prognosis. Five translocations account for approximately 80% of MLL rearrangements: t(4;11)(q21;q23), AFF1/MLL; t(6;11)(q27;q23), MLLT4/MLL; t(9;11)(p22;q23), MLLT3/MLL; t(11;19)(q23;p13.

Karyotype complements the International Prognostic Scoring System for primary myelofibrosis.

Objectives: The International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) is based on five independent predictors of inferior survival: age >65 yr, hemoglobin <10 g/dL, leukocyte count >25 x 10(9)/L, circulating blasts > or =1%, and presence of constitutional symptoms. The presence of 0, 1, 2, and > or =3 adverse factors defines low, intermediate-1, intermediate-2, and high risk disease, respectively. We examined the additional prognostic relevance of karyotype.

Effects of phosphate limitation on expression of genes involved in pyrimidine synthesis and salvaging in Arabidopsis.

Arabidopsis seedlings grown for 14 d without phosphate (P) exhibited stunted growth and other visible symptoms associated with P deficiency. RNA contents in shoots decreased nearly 90%, relative to controls. In shoots, expression of Pht1;2, encoding an inducible high-affinity phosphate transporter, increased threefold, compared with controls, and served as a molecular marker for P limitation.