SNP-array lesions in core binding factor acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia.

Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma

“…Several studies have demonstrated that CCDC26 controls myeloid leukemia cell growth through regulating KIT expression. CCDC26 knockdown upregulated c-KIT mRNA levels [63,64]. Additionally, a study on pancreatic cancer and CDC26 showed that CCDC26 was responsible for the growth and apoptosis of pancreatic cancer cells, partly by regulating PCNA and Bcl2 expression.…”

Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia

“…The prognostic relevance of UPD in CN-AML has not been adequately investigated, although there is evidence that specific UPDs can impact AML patient outcome (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). To better define the utility of UPDs for prognostic risk stratification of CN-AML patients, we herein screened a large cohort of adult de novo CN-AML patients for UPDs and investigated their associations with patient survival and relationship with recurrent gene mutations.…”

Clofarabine Improves Relapse-Free Survival of Acute Myeloid Leukemia in Younger Adults with Micro-Complex Karyotype

“…Bone marrow or peripheral blood samples at diagnosis were analyzed by a Cytoscan HD array (ThermoFisher (Santa Clara, CA, USA)) according to the manufacturer's instructions, as previously described [8]. Data were screened according to the Chromosome Analysis Suite (ChAS) 3.1 software (ThermoFisher), with stringent filters.…”