A second case of trisomy 8 in philadelphia chromosome (Ph)‐negative cells during the course of Ph‐positive chronic myelocytic leukemia

Abstract

A Ph-positive CML patient who had received a peripheral blood stem cell autograft in chronic phase demonstrated a transient regression of the Ph-positive clone with the concurrent appearance of another clone with trisomy 8. This latter clone disappeared when the patient received alpha-interferon.

Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate

“…Alternatively, trisomy 8 may be derived from a constitutional mosaicism. [14][15][16] Some reports suggest that the frequency of such mosaicism in hematologic dysplastic and neoplastic disorders might be as high as 20%. However, constitutional mosaicism for trisomy 8 cannot explain the other abnormalities observed, two of which (monosomy 7 and t(3;10)) are associated with development of myelodysplasia and acute myeloid leukemia.…”

Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8

“…In the remaining 13 cases, the new Ph-negative clones evolved during the chronic phase of CML, and in three cases the new Ph-negative clones were reported as transient. 9,13 In conclusion, the clinical significance of the new phenomenon remains to be further clarified. In analogy with chronic phase CML, in which cytogenetic abnormalities in addition to t(9;22) predicts deterioration of the disease, the Ph-negative unrelated clones must be suspected in the long term to reflect loss of control of the disease.…”

“…The development of new Ph-negative, cytogenetically unrelated clones after therapy of Ph-positive CML with imatinib mesylate is a new phenomenon, [14][15][16] but a few similar cases have previously been observed after therapy with IFN. [8][9][10][11][12][13] In total, at least 17 cases of Phpositive CML developing new Ph-negative clones after therapy with IFN or imatinib mesylate have been reported in the literature ( Table 2). Eleven cases presented a new Ph-negative clone with trisomy 8, and two of these cases also had another Ph-negative unrelated clone with monosomy 7 or del(7q).…”

Induction of centrosome and chromosome aberrations by imatinib in vitro

“…Imatinib treatment will then favor proliferation of these pre-existing clones. 25,26 (ii) The Ph translocation and other cytogenetic abnormalities are induced independently in different progenitor cells. The latter could be due to prodromal CML therapy by administration of cytostatic agents that act as genotoxic drugs.…”