Adult Leukemia Developing after Aplastic Anemia: Report of 8 Cases

Orlandi, Ester; Alessandrino, Emilio Paolo; Caldera, Daniela; Bernasconi, Carlo

doi:10.1159/000205752

Cited by 12 publications

(4 citation statements)

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“…The aetiology of most cases of aplastic anaemia (AA) is unknown. Data are now available that indicate, in some cases, that AA should be considered as a preleukaemic state: (i) AA may reveal a clonal haematopoietic disorder such as paroxysmal nocturnal haemoglobinuria (PNH) (Tooze et al , 1999); (ii) patients treated for AA may develop myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) after immunosuppressive therapy (De Planque et al , 1989; Socié et al , 1993); (iii) a transient phase of AA may precede acute lymphoblastic leukaemia (ALL) in childhood (Breatnach et al , 1981; Matloub et al , 1993; Liang et al , 1994; Hasle et al , 1995) and, in a very few cases, in adults (Nakamori et al , 1986; Orlandi et al , 1988). Data concerning cytogenetic abnormalities in these cases of AA or in primary acquired AA are scarce.…”

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Three cases of typical aplastic anaemia associated with a Philadelphia chromosome

Suzan¹,

Terré

Garcia

et al. 2001

Br J Haematol

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Summary. We report three cases of typical aplastic anaemia (AA) associated with a Philadelphia chromosome. This translocation was detected at the time of diagnosis of AA (one patient) and when overt leukaemia was diagnosed (two patients: one chronic myeloid leukaemia and one acute lymphoblastic leukaemia) after AA therapy and recovery of blood counts. We discuss the literature arguments about considering some cases of AA as preleukaemic disorders and suggest that our cases illustrate the association of AA with a clonal malignant disorder. We conclude that cytogenetic analysis is necessary at diagnosis of AA or after recovery of blood counts.

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Three cases of typical aplastic anaemia associated with a Philadelphia chromosome

Suzan¹,

Terré

Garcia

et al. 2001

Br J Haematol

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“…Examples are numerous. For instance, myelodysplas c syndromes (MDS) o en precede by years (some mes by decades) the development of overt leukemia [1181,1182]. MDS by itself may cause poten ally life-threatening symptoms (anemia, thrombocytopenia, agranulocytopenia, etc.).…”

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confidence: 99%

DNA repair systems

Chakarov¹,

Petkova²,

Russev³

2014

Biodiscovery

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This paper provides detailed insight into the mechanisms of repair of different types of DNA damage and the direct molecular players (enzymes repairing the damage or tagging the damaged site for further processing; damage sensor molecules; other signalling and effector molecules). The gene c bases of diseases and condi ons associated with defec ve DNA repair are comprehensively reviewed, from the 'classic' severe diseases such as xeroderma pigmentosum and Cockayne syndrome to the much more subtle UV sensi vity syndromes. The review analyses the basic molecular mechanisms underlying the rela vely rare monogenic diseases of DNA repair and management of genome integrity as well as the common mul factorial diseases and condi ons with late onset that are associated with increased levels of oxida ve stress (metabolic syndrome, diabetes type 2, cardiovascular disease) and with accumula on of 'errors' in DNA (normal and pathological ageing phenotypes, various cancers). The role of cell cycle checkpoints in dividing cells and the mechanisms of decision-making for the fate of a damaged cell are discussed with regards to the cell homeostasis in normal and cancerous ssues. The role of major DNA damageassociated signalling and effector molecules (p53, ATM, poly-(ADP-ribose)-polymerase, DNA-dependent protein kinase, BRCA proteins, re noblastoma protein, and others) is discussed and illustrated with examples in the context of health and disease. DNA repair and programmed cell death are viewed together as a unified mechanism for limi ng the presence of damaged cells and cells with poten ally oncogenic transforma on in mul cellular organisms. Special a en on is paid to ageing as a natural phenomenon and an adap ve evolu onary mechanism, with a brief outline of 'successful ageing'. The differen al rates of repair of DNA in transcribed and nontranscribed regions of the genome and the specifici es of DNA repair profile in some types of cells (terminally differen ated cells, pluripotent stem cells, etc.) and in certain taxonomic groups (e.g. 'the rodent repairadox') are discussed with regards to replica ve ageing and the evolu onary processes on microand macroscale. The role of mutagenesis as a 'hit and miss' mechanism and the 'leakiness' of DNA repair for increasing gene c diversity in the course of individual life and on evolu onary scale and the phenomenology of ongoing molecular evolu on are extensively reviewed. Conflict of Interests:No poten al conflict of interest was disclosed by any of the authors. Types of DNA repair systemsIf you wish for peace, prepare for war.Publius Flavius Vege us Renatus, De Re Militari (circa 380 AD).DNA damage is a very broad term, encompassing many different types of lesions in DNA.Accordingly, DNA repair comprises many different types of pathways and mechanisms covering virtually every possible type of injury to the sequence or the structure of DNA.Accep ng Lewin's defini on of DNA damage "... any change that introduces a devia on from the usual double-helical structure" [1] , we may pre...

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“…examples are numerous. it is well known from clinical practice that myelodysplastic syndromes (MDS) often precede (sometimes by decades) the development of overt leukemia (59,78). Myelodysplasias may produce potentially life-threatening incidents on their own (e.g.…”

Section: Back In My Day We Didn't Have This: the Emergence Of Aging-rmentioning

confidence: 99%