Myelodysplasia in a patient with pre‐existing paroxysmal nocturnal haemoglobinuria: a clonal disease originating from within a clonal disease

Abstract

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia; more rarely to a myelodysplastic syndrome (MDS) or to acute myeloid leukaemia (AML). We have studied a patient who suffered from PNH and later developed refractory anaemia with ringed sideroblasts (RARS) associated with trisomy 8. By testing peripheral blood cells with appropriate antibodies we have shown that all of the red cells, neutrophils and monocytes, as well as 20% of the lymphocytes, belonged to the PNH clone; in contrast, only 43% of neutrophils and 22% of monocytes belonged to the MDS clone. We infer that the MDS must have arisen from within the PNS clone.

Trisomy 8 in a patient who responded to therapy with all‐trans‐retinoic acid and developed paroxysmal nocturnal haemoglobinuria

“…However, from the available data in the literature, PNH can be regarded as a preleukaemic lesion. FISH analysis of previous cases showed that the MDS clone must have arisen from within the PNH clone, and the karyotypic change of the MDS clone took place in a cell that was less multipotent than that from which the PNH clone arose (Longo et al, 1994). In our case it seems that either different clones were simultaneously affected by genetic lesions or the PNH clone was developed later in the course of the disease.…”

“…In the literature, two cases of trisomy 8 have been reported in association with PNH (Longo et al, 1994;Parlier et al, 1992). The patient reported proves that the bone marrow cells were generally prone to somatic mutations and myelodysplasia did not evolve from the PNH clone.…”

Paroxysmal nocturnal hemoglobinuria clone in a case of myelodysplastic syndrome rapidly progressing to acute leukemia

“…A review of literature presents confl icting views. Van Kamp et al documented presence of GPI anchored proteins on MDS cells whereas Nakahata et al and Longo et al demonstrated that the leukemic blasts arose from GPI anchored defi cient cells [7][8][9]. The majority of neutrophils in our case were dysplastic which also lacked GPI anchored proteins, thus favoring a common pathogenetic origin of myelodysplastic and PNH clone.…”

Chromosomal Aberrations and HMGA2 Expression in Paroxysmal Nocturnal Hemoglobinuria

“…However, no translocation was detected, demonstrating that this event is not common in PNH. In patients with concomitant PNH and MDS, other studies have found trisomy 8 in the fraction of GPI-deficient cells, suggesting that the PIGA mutation affected the stem cell first, and chromosomal aberrations evolved within a subclone thereafter [5,33,34]. Recently, it was shown that a stochastic model of clonal stem cell evolution could capture some of the features of PNH [35].…”