Complex rearrangement in acute myeloid leukemia M2 with RUNX1/RUNX1T1 fusion involving chromosomes 8, 17 and 21.

Background: The translocation t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML) sub type M2. About 3-5 % of cases with additional chromosomal abnormalities, including structural and numerical ones, are reported to include a complex translocation t(8;21;N).

Case Presentation: Here we report a chromosome rearrangement observed in a 19 years-old female diagnosed with AML-M2.

A new childhood ALL case with an extremely complex karyotype and acute spontaneous tumor lysis syndrome.

Background: B cell precursor acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood, with, after corresponding treatment, an overall complete remission rate of 90%. Approximately 75% of B-ALL cases harbor recurrent abnormalities, including so-called complex karyotypes (CK). Tumor lysis syndrome (TLS) is a metabolic abnormality which may arise during cancer therapy and also, extremely rarely, as spontaneous TLS before initiation of chemotherapy in patients with ALL.

An acquired stable variant of a dicentric dic(9;20) and complex karyotype in a Syrian childhood B-acute lymphoblastic leukemia case.

Background: About 25 years ago, the acquired chromosome abnormality dicentric dic(9;20)(p11 ~ 13;q11) was seen described as a non-random aberration in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet, about 200 cases were reported. However, dicentric dic(9;20) is a subtle abnormality which easily may be mixed up with monosomy 20 and/or del(9p).

Complex karyotype with cryptic gene rearrangement and deletion of and genes in childhood B-cell acute lymphoblastic leukemia: A case report.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. B-ALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of B-ALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen.

An Original Complex Rearrangement Involving Chromosomes 9, 11, and 14, Harboring a Complex KMT2A Gene Rearrangement in an Infant With Mixed-phenotype Acute Leukemia.

KMT2A gene rearrangements represent the most frequent group of abnormalities in childhood leukemia (~70% of cases), with over 120 rearrangements described. The investigation of KMT2A rearrangements is still a vast field to be explored. Several studies have been characterizing different outcomes and leukemogenic mechanisms, depending on the translocation partner gene involved in childhood KMT2A-r leukemias.

Molecular cytogenetic pilot study on pleomorphic adenomas of salivary glands.

Pleomorphic adenomas (PAs) of salivary glands are the most frequent entity of solid parotid tumors. Nonetheless, their genetics is not yet well understood. Thus, the current study characterized 14 PAs using a unique combination of cytogenetic, molecular cytogenetic and/or molecular karyotyping based approaches.

A New Complex Karyotype Involving a KMT2A-r Variant Three-Way Translocation in a Rare Clinical Presentation of a Pediatric Patient with Acute Myeloid Leukemia.

Patients with childhood acute myeloid leukemia (AML) with complex karyotypes (CKs) have a dismal outcome. However, for patients with a KMT2A rearrangement (KMT2A-r), the prognosis appears to depend on the fusion partner gene rather than the karyotype structure. Thus, a precise characterization of KMT2A-r and the fusion partner genes, especially in CKs, is of interest for managing AML.

A new adult AML case with an extremely complex karyotype, remission and relapse combined with high hyperdiploidy of a normal chromosome set in secondary AML.

Background: Chromosomal abnormalities are diagnostic and prognostic key factors in acute myeloid leukemia (AML) patients, as they play a central role for risk stratification algorithms. High hyperdiploidy (HH), a rare cytogenetic abnormality seen commonly in elder male AML patients, is normally categorized under AML with complex karyotype (CK). Accordingly, patients with HH generally are associated with low remission rates and a short overall survival.

Parental origin of deletions and duplications - about the necessity to check for cryptic inversions.

Background: Copy number variants (CNVs) are the genetic bases for microdeletion/ microduplication syndromes (MMSs). Couples with an affected child and desire to have further children are routinely tested for a potential parental origin of a specific CNV either by molecular karyotyping or by two color fluorescence in situ hybridization (FISH), yet. In the latter case a critical region probe (CRP) is combined with a control probe for identification of the chromosome in question.

Molecular approaches identify a cryptic MECOM rearrangement in a child with a rapidly progressive myeloid neoplasm.

Myeloid neoplasms are a heterogeneous group of hematologic disorders with divergent patterns of cell differentiation and proliferation, as well as divergent clinical courses. Rare recurrent genetic abnormalities related to this group of cancers are associated with poor outcomes. One such abnormality is the MECOM gene rearrangement that typically occurs in cases with chromosome 7 abnormalities.

A unique set of complex chromosomal abnormalities in an infant with myeloid leukemia associated with Down syndrome.

Background: Children with Down syndrome (DS) have an enhanced risk of developing acute leukemia, with the most common subtype being acute megakaryoblastic leukemia (AMKL). Myeloid leukemia in Down syndrome (ML-DS) is considered a disease with distinct clinical and biological features. There are few studies focusing on the clonal cytogenetic changes during evolution of ML-DS.

GAS6 Oncogene and Reverse MLLT3-KMT2A Duplications in an Infant with Acute Myeloid Leukemia and a Novel Complex Hyperdiploid Karyotype: Detailed High-Resolution Molecular Cytogenetic Studies.

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous disease, presenting cytogenetic and molecular abnormalities which turned out to be critical prognostic factors. Ploidy changes as gain or loss of individual chromosomes are rare in AML, occurring only in about 1-2% of the affected children. Hyperdiploid karyotypes are exceedingly rare in infants less than 12 months of age.

Multicolor Karyotyping and Fluorescence In Situ Hybridization-Banding (MCB/mBAND).

Multicolor fluorescence in situ hybridization (mFISH) approaches are routine applications in tumor as well as clinical cytogenetics nowadays. The first approach when thinking about mFISH is multicolor karyotyping using human whole chromosome paints as probes; this can be achieved by narrow-band filter-based multiplex-FISH (M-FISH) or interferometer/spectroscopy-based spectral karyotyping (SKY). Besides, various FISH-based banding approaches were reported in the literature, including multicolor banding (MCB/mBAND) the latter being evaluated by narrow-band filters, and using specific software.

Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes.

In pediatric acute leukemias, reciprocal chromosomal translocations frequently cause gene fusions involving the lysine (K)-specific methyltransferase 2A gene (KMT2A, also known as MLL). Specific KMT2A fusion partners are associated with the disease phenotype (lymphoblastic vs. myeloid), and the type of KMT2A rearrangement also has prognostic implications.

BIRC3 alterations in chronic and B-cell acute lymphocytic leukemia patients.

Deletions within chromosome 11q22-23, are considered among the most common chromosomal aberrations in chronic lymphocytic leukemia (CLL), and are associated with a poor outcome. In addition to the ataxia telangiectasia mutated () gene, the baculoviral IAP repeat-containing 3 () gene is also located in the region. encodes a negative regulator of the non-canonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein.

A novel gene rearrangement associated with / deletion in young adult B-cell acute lymphoblastic leukemia.

Acquired copy number changes are common in acute leukemia. They are reported as recurrent amplifications or deletions (del), and may be indicative of involvement of oncogenes or tumor suppressor genes in acquired disease, as well as serving as potential biomarkers for prognosis or as targets for molecular therapy. The present study reported a gain of copy number of 14q13 to 14q32, leading to immunoglobulin heavy chain locus splitting in a young adult female.

Molecular cytogenetic studies characterizing a novel complex karyotype with an uncommon 5q22 deletion in childhood acute myeloid leukemia.

Deletions in the long arm of chromosome 5 or loss of the whole chromosome are rare in childhood Acute Myeloid Leukemia (AML) patients. It is also unknown if the wide variety of breakpoints have diverging implications in the patient's outcome. Despite -5/5q- abnormalities have usually been described as a poor prognostic feature, however, the low frequency of -5/5q- in pediatric AML patients limits a full knowledge about this cytogenetic and clinical category, which is an intriguing factor for further research and new findings.

High rates of submicroscopic aberrations in karyotypically normal acute lymphoblastic leukemia.

Background: Acute lymphoblastic leukemia (ALL) is not a single uniform disease. It consists of several subgroups with different cytogenetic and molecular genetic aberrations, clinical presentations and outcomes. Banding cytogenetics plays a pivotal role in the detection of recurrent chromosomal rearrangements and is the starting point of genetic analysis in ALL, still.

A cryptic three-way translocation t(10;19;11)(p12.31;q13.31;q23.3) with a derivative Y-chromosome in an infant with acute myeloblastic leukemia (M5b).

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the malignant transformation of hematopoietic precursors to a pathogenic cell clone. Chromosomal band 11q23 harboring MLL (=mixed lineage leukemia) gene is known to be involved in rearrangements with variety of genes as activating partners of MLL in different AML subtypes. Overall, an unfavorable prognosis is associated with MLL abnormalities.

Novel Cryptic Rearrangements in Adult B-Cell Precursor Acute Lymphoblastic Leukemia Involving the MLL Gene.

MLL (mixed-lineage-leukemia) gene rearrangements are typical for acute leukemia and are associated with an aggressive course of disease, with a worse outcome than comparable case, and thus require intensified treatment. Here we describe a 69-year-old female with adult B cell precursor acute lymphoblastic leukemia (BCP-ALL) with hyperleukocytosis and immunophenotype CD10- and CD19+ with cryptic MLL rearrangements. G-banding at the time of diagnosis showed a normal karyotype: 46,XX.

The current state of molecular cytogenetics in cancer diagnosis.

Cytogenetics and molecular cytogenetics are and will continue to be indispensable tools in cancer diagnostics. Leukemia and lymphoma diagnostics are still emphases of routine (molecular) cytogenetics and corresponding studies of solid tumors gain more and more prominence. Here, first a historical perspective of molecular tumor cytogenetics is provided, which is followed by the basic principles of the fluorescence in situ hybridization (FISH) approach.

Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case.

Background: Chronic myeloid leukemia (CML) is genetically characterized by the occurrence of a reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22, i.e. the Philadelphia (Ph) chromosome.

MLLT10 and IL3 rearrangement together with a complex four-way translocation and trisomy 4 in a patient with early T-cell precursor acute lymphoblastic leukemia: A case report.

Cytogenetic classification of acute lymphoblastic leukemia (ALL) is primarily based on numerical and structural chromosomal abnormalities. In T-cell ALL (T-ALL), chromosomal rearrangements are identified in up to 70% of the patients while the remaining patients show a normal karyotype. In the present study, a 16-year-old male was diagnosed with T-precursor cell ALL and a normal karyotype after standard GTG-banding, was studied retrospectively (>10 years after diagnosis) in frame of a research project by molecular approaches.