RUNX1 amplification in AML with myelodysplasia‐related changes and ring 21 chromosomes

Abstract

Ring 21 is an unstable structural abnormality of chromosome 21 that can lead to RUNX1 gene amplification. We present a unique case with a carrier patient of a constitutional ring chromosome 21 (partial monosomy and trisomy 21) with dysmorphic features and congenital malformations phenotype, who developed acute myeloid leukaemia with myelodysplasia-related changes and two ring 21 chromosomes with RUNX1 amplification. The patient's constitutional ring 21 chromosome showed alterations in tumour suppressor genes, and oncogenes, but not in RUNX1. RUNX1 gene expression at acute myeloid leukaemia diagnosis, showed no upregulation, so other genes may also be the genetic amplification targets in this patient. Copyright © 2016 John Wiley & Sons, Ltd.

21q22 amplification detection in three patients with acute myeloid leukemia: cytogenomic profiling and literature review

“…21q22 amplification by RUNX1 FISH is rare in AML with a reported prevalence of 0.1% [14]. Most were identified by cytogenetically visible abnormal 21q or "incidental" findings by RUNX1 FISH [7][8][9][10][11][12][13][14]. Due to this limitation, the true incidence of 21q22 amplification in AML remains elusive.…”

“…More recently, amplification of 21q22, defined as five or more copies per cell, has emerged as a rare cytogenomic aberration in AML. Gain of 21q22 has been reported in a limited number of AML patients, primarily case reports of adults featuring complex karyotypes [7][8][9][10][11][12][13][14]. The largest reported cohort contained 13 patients and the authors observed that 21q22 amplification was associated with reduced survival [14].…”

The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes

“… 109 , 110 Patients of RC 11 associated with Wilms tumor, RC 13 with retinoblastoma, RC 17 with neurofibromatosis, RC 21 with acute myeloid leukemia, and RC 22 with neurofibromatosis, meningiomas, and vestibular schwannoma have been reported. 85 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 Dynamic mosaicism and dysfunction of harbored tumor suppressor genes in these constitutional RCs mediated the predisposition to cancer. 119 Cancer surveillance should be considered for patients carrying these RCs.…”

“… 112 17 TP53 , NF1 neurofibromatosis type 1 Havlovicova et al. 85 21 RUNX1 acute myeloid leukemia Burillo-Sanz et al., 113 Vormittag-Nocito et al. 114 22 NF2 neurofibromatosis type II, meningiomas, schwannoma, Tommerup et al., 115 Petrella et al., 116 Denayer et al.…”

RUNX family: Oncogenes or tumor suppressors (Review)

“…The contrasting roles of RUNX proteins can be explained by generating specific biological contexts for lineage and cancer or the developmental stage at which these abnormalities have been detected. For example, myeloid leukemia cases are associated with chromosome 21 polysomies and with RUNX1 amplification (216). In addition, lymphoid neoplasms have been demonstrated to be activated by the proviral insertion murine RUNX genes and RUNX1 amplification in humans (32).…”