Cytogenetic evolution patterns in CML post-SCT

Abstract

The cytogenetic evolution patterns in chronic myeloid leukemia (CML) after allogeneic (allo) stem cell transplantation (SCT) are different from the ones observed in non-transplanted patients, a phenomenon suggested to be caused by the conditioning regime. We reviewed 131 CMLs displaying karyotypic evolution after SCT (122 allo, nine autologous (auto)), treated at Lund University Hospital or reported in the literature. Major route abnormalities (i.e., þ 8, þ Ph, i(17q), þ 19, þ 21, þ 17 and À7) were seen in 14%, balanced aberrations in 61%, hyperdiploidy in 19%, pseudodiploidy in 79%, divergent clones in 14%, and Ph-negative clones in 21%. The breakpoints involved in secondary structural rearrangements clustered at 1q21, 1q32, 7q22, 9q34, 11q13, 11q23, 12q24, 13q14, 17q10 and 22q11. Cytogenetic abnormalities common in AML after genotoxic exposure, that is, der(1;7)(q10;p10), del(3p), À5, del(5q), À7, À17, der(17p), À18, and À21, were only rarely seen post-SCT. Comparing the cytogenetic features in relation to type of SCT revealed that balanced aberrations were significantly more common after allo than after auto SCT (64 and 22%, respectively, P ¼ 0.03). In addition, there was a trend as regards hyperdiploidy being more common after auto (P ¼ 0.07) and pseudodiploidy being more frequent after allo SCT (P ¼ 0.09). Possible reasons for these differences are discussed.

Karyotypic findings in chronic myeloid leukemia cases undergoing treatment

“…All of these patients were in chronic phase of CML [Table 4]. Similar observations were made by Karrman et al .,[12] after allogeneic stem cell transplantation; major route abnormalities (i.e., +8, +Ph, i(17q), +19, +21, +17, and -7) were present. Information regarding the impact of specific types of additional cytogenetic abnormalities is still limited.…”

RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity

“…Interestingly, 1q32 anomalies, which include Jarid1b, are common genetic mutations found in cells of chronic myeloid leukemia patients during disease progression, which is characterized by a block in myeloid differentiation. 39,40 This observation supports the hypothesis that low Jarid1b levels maintain stem cell fate that, combined with BCR-ABL-induced proliferation, could result in development of overt leukemia. In our studies, transplant recipients of shJarid1b-transduced cells never developed leukemia.…”

Similar patterns of chromosome abnormalities in CML occur in addition to the Philadelphia chromosome with or without tyrosine kinase inhibitor treatment

“…This differs from previous observations in recipients of allogeneic stem cell transplantation (SCT), as differences in the cytogenetic evolution patterns had been observed compared with patients who received conventional treatment. In the study of Karrman et al, 7 there was a lower frequency of major route abnormalities in recipients of allogeneic SCT (15%) when compared with those patients having received an autologous SCT (two from three patients with Ph þ clones). Chase et al 8 reported a high frequency of translocations and deletions involving 13q in recipients of allo-SCT who showed relapse or persistent disease.…”