Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF

Jahns-Streubel, G.; Braess, Jan; Schoch, Claudia; Fonatsch, Christa; Haase, Detlef; Binder, Claudia R.; Wörmann, Bernhard; Büchner, Thomas; Hiddemann, Wolfgang

doi:10.1038/sj.leu.2402029

Cited by 17 publications

(17 citation statements)

References 41 publications

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“…High levels correlated with poor response to chemotherapy [56,57] and short duration disease free survival [56,58] . Contrasting results were obtained in another study where spontaneous proliferative determined by tritiated thymidine incorporation was significantly higher in favourable karyotypes compared to cases with unfavorable cytogenetics [59] .…”

Section: Abdullah M Unapplied Markers In Amlcontrasting

confidence: 69%

“…Proliferative activity of AML blasts were significantly higher in favourable karyotypes compared to unfavourable karyotypes. Exposure to GM-CSF significantly increased proliferation in normal and unfavarouble groups compared to favourable karyotype [59] . CD34+ expression of cells from AML bone marrow were significantly reduced following incubation with a cytokine mix without affecting viability in all samples analysed.…”

Section: Abdullah M Unapplied Markers In Amlmentioning

confidence: 92%

“…Complete remission is achievable in 65% de novo AML and 41% secondary AML. Median overall survival for these patients was 1119 days for age 16-55 years (N=554), 350 days for age [56][57][58][59][60][61][62][63][64][65] years (N = 437) and 80 days for patients aged 76-89 year old (N = 968) [1] . The French-American-British (FAB) classification of acute myeloid leukemias, the first classification established more than 40 years ago, identifies eight subtypes (M0-M7) based on morphology and cytochemistry staining.…”

Section: Introductionmentioning

confidence: 99%

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Less Utilized Prognostic Markers in Acute Myeloid Leukemia

Abdullah

2016

International Journal of Hematology Research

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Acute myeloid leukemia (AML) results from the over-proliferation of progenitor cells of the myeloid lineage in the bone marrow. It is a heterogeneous disease that is aggressive and difficult to treat. AML diagnosis is based on clinical as well as laboratory investigations. Risk stratification is important to assess risk of relapse. Current guidelines for risk stratification are dependent on identification of genetic aberrations particularly chromosomal translocations and gene mutations. Though these are observed in the majority of patients, the best treatment regimen remains elusive. AML blasts are assumed to have transformed from a normal counterpart and maintains many normal regulatory functions. Early features such as stem cell properties has long been proven to be linked to early relapse in AML. Leukaemia stem cells (LSC) are identified by high CD34 and negative CD38 expression. Aberrant expression of a third marker such as Thy-1/CD90 negativity, expression of CLL-1 and IL-3R (CD123), intermediate levels of aldehyde dehydrogenase and co-expression of common chromosomal translocation may be used to distinguish from normal hematopoietic stem cells. In vitro characteristics of AML blasts such as proliferation, survival or response to treatment are also able to predict patient response to therapy, replicative of its interaction with the microenvironment. These potential prognostic markers are well studied but are currently not considered in patient management.

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Section: Abdullah M Unapplied Markers In Amlcontrasting

confidence: 69%

Section: Abdullah M Unapplied Markers In Amlmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Less Utilized Prognostic Markers in Acute Myeloid Leukemia

Abdullah

2016

International Journal of Hematology Research

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“…This is important, since chemoresistance mediated by both of these mechanisms is potentially amenable to modulation, which could lead to significant improvements in clinical outcome. Further evidence supporting the notion that karyotype analysis identifies subgroups of AML that are biologically similar irrespective of the age of the patient has been provided by recent studies reporting a close correlation between cytogenetic subgroup and bax/bcl2 ratio, 31 immunophenotypic profile, 32 and the behavior of primary leukemic blasts, both in vitro, in terms of proliferative activity, semisolid colony growth, and response to granulocyte-macrophage colony-stimulating factor, 33,34 and in vivo, influencing engraftment characteristics in nonobese diabetic/ severe combined immunodeficient mice. 35 To date, cytogenetic classification systems used to predict outcome in AML have been somewhat inconsistent.…”

Section: Discussionmentioning

confidence: 82%

The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial

Grimwade

2001

Blood

840

612

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Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification is frequently based upon diagnostic karyotype, which was the most important prognostic factor in the UK Medical Research Council (MRC) AML10 trial. Considered here is whether karyotype is also predictive in older adults; this is done by studying 1065 cases from MRC AML11 (median age, 66 years). Three prognostic groups were distinguished on the basis of response to induction therapy and overall survival (OS). Those with t(15; 17), t(8;21), or inv(16) composed the favorable risk group. Overall, these abnormalities predicted a superior complete remission (CR) rate (72%), reflecting relatively low levels of resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with superior OS (34% at 5 years). Normal karyotype (CR, 63%; RD, 17%; RR, 78%; OS, 15%) and other noncomplex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%) composed the intermediate group; while complex karyotype predicted an extremely poor prognosis (CR, 26%; RD, 56%; RR, 91%; OS, 2%). Combining MRC AML10 and AML11 (n ‫؍‬ 2677) revealed that the most favorable changes were rarer in older patients (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities were more common (6% vs 13%). This study suggests that hierarchical cytogenetic classification identifies biologically distinct subsets of AML that are represented in all age groups. Furthermore, it highlights the importance of karyotype as a critical independent determinant of outcome in older patients with AML, providing a potential framework for stratified treatment approaches. (Blood. 2001;98: 1312-1320)

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“…The group with favorable cytogenetics benefits more from cytarabine dose escalation in induction therapy (Burnett AK et al Br J Haemtol 1996; 93(Suppl 2): 313; abstract) [59][60][61] and from HDAC in consolidation therapy. 62,63 Jahns et al 64 reported the findings of cell-cycle studies of the blast cells from different cytogenetic risk groups. 64 Blast cells from patients with a favorable karyotype had a high level of spontaneous proliferative activity and were not responsive to growth stimulatory cytokines, while blasts from most patients with an unfavorable karyotype had a low level of spontaneous proliferative activity and were sensitive to HGF growth stimulation.…”

Section: Discussionmentioning

confidence: 99%