title: Chromosome anomalies in bone marrow as primary cause of aplastic or hypoplastic conditions and peripheral cytopenia: disorders due to secondary impairment of RUNX1 and MPL genes.
abstract: BACKGROUND
  Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS.
  
  
  RESULTS
  Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2-8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT).
  
  
  CONCLUSIONS
  A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias.
authors.affiliation: Biologia e Genetica, Dipartimento di Medicina Clinica e Sperimentale, Università dell'lnsubria, Varese, Italy. emanuela.maserati@uninsubria.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marletta
authors.forename: Roberto
authors.initials: R
authors.lastname: Valli
authors.forename: Barbara
authors.initials: B
authors.lastname: Pressato
authors.forename: Lydia
authors.initials: L
authors.lastname: Mare
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalbano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Loffredo
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.forename: Luciana
authors.initials: L
authors.lastname: Vinti
authors.forename: Simona
authors.initials: S
authors.lastname: Ferrari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Cesare-Merlone
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Curto
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati