Therapy of Blastic Transformation of Chronic Myeloid Leukemia

Leukemias ◽  
1993 ◽  
pp. 249-255
Author(s):  
S. Pawelski ◽  
L. Konopka ◽  
K. Szczepanik ◽  
H. Zdziechowska
Haematologica ◽  
2011 ◽  
Vol 97 (3) ◽  
pp. 473-474 ◽  
Author(s):  
D. Milojkovic ◽  
A. Ibrahim ◽  
A. Reid ◽  
L. Foroni ◽  
J. Apperley ◽  
...  

2020 ◽  
Vol 21 (4) ◽  
pp. 1177 ◽  
Author(s):  
Popp ◽  
Kohl ◽  
Naumann ◽  
Flach ◽  
Brendel ◽  
...  

DNA damage and alterations in the DNA damage response (DDR) are critical sources of genetic instability that might be involved in BCR-ABL1 kinase-mediated blastic transformation of chronic myeloid leukemia (CML). Here, increased DNA damage is detected by γH2AX foci analysis in peripheral blood mononuclear cells (PBMCs) of de novo untreated chronic phase (CP)-CML patients (n = 5; 2.5 γH2AX foci per PBMC ± 0.5) and blast phase (BP)-CML patients (n = 3; 4.4 γH2AX foci per PBMC ± 0.7) as well as CP-CML patients with loss of major molecular response (MMR) (n = 5; 1.8 γH2AX foci per PBMC ± 0.4) when compared to DNA damage in PBMC of healthy donors (n = 8; 1.0 γH2AX foci per PBMC ± 0.1) and CP-CML patients in deep molecular response or MMR (n = 26; 1.0 γH2AX foci per PBMC ± 0.1). Progressive activation of erroneous non-homologous end joining (NHEJ) repair mechanisms during blastic transformation in CML is indicated by abundant co-localization of γH2AX/53BP1 foci, while a decline of the DDR is suggested by defective expression of (p-)ATM and (p-)CHK2. In summary, our data provide evidence for the accumulation of DNA damage in the course of CML and suggest ongoing DNA damage, erroneous NHEJ repair mechanisms, and alterations in the DDR as critical mediators of blastic transformation in CML.


Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 652-657 ◽  
Author(s):  
R Bernstein ◽  
A Bagg ◽  
M Pinto ◽  
D Lewis ◽  
B Mendelow

Abstract Two patients with acute blastic transformation of chronic myeloid leukemia (CML) associated with strikingly elevated platelet counts showed abnormalities of chromosome 3q in addition to the standard Philadelphia (Ph1) chromosome translocation. The first patient had an inversion of chromosome 3 (q21q26) cytologically identical to an inversion 3 previously reported in de novo acute megakaryoblastic leukemia, and the second patient showed a translocation between chromosome 3q and the chromosome 9 homologue not involved in the Ph1 translocation, [t(3;9)(q21;q34)]. Previous studies had incriminated either 3q21 or 3q26 as the locus for a regulatory thrombopoietic gene, but the current study suggests that 3q21 is the relevant site.


Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2304-2309 ◽  
Author(s):  
Jyoti Wadhwa ◽  
Richard M. Szydlo ◽  
Jane F. Apperley ◽  
Andrew Chase ◽  
Marco Bua ◽  
...  

We analyzed factors having an impact on response to treatment and survival in 78 consecutive patients with chronic myeloid leukemia (CML) in blastic transformation (BT) referred to the Hammersmith Hospital from January 1995 to December 2000. BT was defined as the presence of at least 30% blasts in blood or marrow or extramedullary blastic deposits. Immunophenotyping of blasts showed 57 myeloid, 19 lymphoid, and 2 biphenotypic. The median age of the patients was 39.1 years (range, 11.3-73.4 years), with 55 males and 23 females. The median survival for all patients after onset of BT was 8.2 months (95% CI, 6.4-10). Patients in lymphoid BT survived longer than those in myeloid BT (median, 11.2 months versus 6.9 months, P = .052). Initial treatment varied; 41 patients received cytotoxic drugs, 8 underwent allogeneic or autologous transplantation procedures, 21 received STI571 (imatinib mesylate, Gleevec), 1 received radiotherapy, and 7 received no therapy. Of the 25 (32%) patients who achieved a “second chronic phase” with first therapy, 6 of 21 (29%) were treated with STI571 and 19 of 50 (38%) were treated with chemotherapy, transplantation, or radiotherapy. Patients who achieved a second chronic phase survived longer than those who did not (median time from onset of BT 12.0 months versus 6.3 months, P = .0004). In multivariate analysis the finding of more than 50% blast cells in the blood and the presence of cytogenetic progression were independent adverse prognostic variables for survival. We conclude that survival after onset of BT has improved in recent years but is still unsatisfactory. We speculate that the combined use of STI571 with cytotoxic drugs may offer additional benefit.


1991 ◽  
Vol 11 (3) ◽  
pp. 271-275 ◽  
Author(s):  
George T. Roberts ◽  
M. Andrew Padmos ◽  
Hugh Clink ◽  
David G. Spence ◽  
Peter Ernst ◽  
...  

1999 ◽  
Vol 26 (10) ◽  
pp. 497-503 ◽  
Author(s):  
Steven Kaddu ◽  
Christine Beham-Schmid ◽  
Paul Zenahlik ◽  
Helmut Kerl ◽  
Lorenzo Cerroni

2010 ◽  
Vol 120 (7) ◽  
pp. 2254-2264 ◽  
Author(s):  
Danilo Perrotti ◽  
Catriona Jamieson ◽  
John Goldman ◽  
Tomasz Skorski

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