Cytogenetic abnormalities, WHO classification, and evolution of children and adolescents with acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, which is heterogeneous in terms of morphological, cytogenetic and clinical features. Cytogenetic abnormalities, including karyotype aberrations, gene mutations and gene expression abnormalities are the most important diagnostic tools in diagnosis, classification and prognosis in acute myeloid leukemias. Based on World Health Organization (WHO) classification, acute myeloid leukemias can be divided to four groups. Due to the heterogeneous nature of AML and since most therapeutic protocols in AML are based on genetic alterations, gathering further information in the field of rare disorders as well as common cytogenetic abnormalities would be helpful in determining the prognosis and treatment in this group of diseases. Recently, the role of microRNAs (miRNAs) in both normal hematopoiesis and myeloid leukemic cell differentiation in myeloid lineage has been specified. miRNAs can be used instead of genes for AML diagnosis and classification in the future, and can also play a decisive role in the evaluation of relapse as well as response to treatment in the patients. Therefore, their use in clinical trials can affect treatment protocols and play a role in therapeutic strategies for these patients. In this review, we have examined rare cytogenetic abnormalities in different groups of acute myeloid leukemias according to WHO classification, and the role of miRNA expression in classification, diagnosis and response to treatment of these disorders has also been dealt with.

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Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies

Blood ◽

10.1182/blood-2011-07-367508 ◽

2012 ◽

Vol 119 (2) ◽

pp. 551-558 ◽

Cited By ~ 103

Author(s):

Sabine Kayser ◽

Manuela Zucknick ◽

Konstanze Döhner ◽

Jürgen Krauter ◽

Claus-Henning Köhne ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Who Classification ◽

World Health ◽

Prognostic Impact ◽

Cytogenetic Abnormalities ◽

Allogeneic Hsct ◽

Monosomal Karyotype ◽

Acute Myeloid

We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK+ patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK+. MK+ patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of −5/5q−, −7, 7q−, abnl(12p), abnl(17p), −18/18q−, −20/20q−, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)–related cytogenetic abnormalities (P < .0001, each); and NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and tyrosine kinase domain mutations (P = .02) were less frequent in MK+. Response to induction therapy and overall survival in MK+ patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients, allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival.

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NPM1 mutation but not RUNX1 mutation or multilineage dysplasia defines a prognostic subgroup within de novo acute myeloid leukemia lacking recurrent cytogenetic abnormalities in the revised 2016 WHO classification

American Journal of Hematology ◽

10.1002/ajh.24739 ◽

2017 ◽

Vol 92 (7) ◽

pp. E123-E124 ◽

Cited By ~ 5

Author(s):

Olga K. Weinberg ◽

Christopher J. Gibson ◽

Traci M. Blonquist ◽

Donna Neuberg ◽

Olga Pozdnyakova ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Who Classification ◽

De Novo ◽

Npm1 Mutation ◽

Cytogenetic Abnormalities ◽

Multilineage Dysplasia ◽

Runx1 Mutation ◽

Acute Myeloid

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Association of mutations with morphological dysplasia in de novo acute myeloid leukemia without 2016 WHO Classification-defined cytogenetic abnormalities

Haematologica ◽

10.3324/haematol.2017.181842 ◽

2018 ◽

Vol 103 (4) ◽

pp. 626-633 ◽

Cited By ~ 7

Author(s):

Olga K. Weinberg ◽

Christopher J. Gibson ◽

Traci M. Blonquist ◽

Donna Neuberg ◽

Olga Pozdnyakova ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Who Classification ◽

De Novo ◽

Cytogenetic Abnormalities ◽

Acute Myeloid

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Less Toxicity by Optimizing Chemotherapy, but Not by Addition of Granulocyte Colony-Stimulating Factor in Children and Adolescents With Acute Myeloid Leukemia: Results of AML-BFM 98

Yearbook of Oncology ◽

10.1016/s1040-1741(08)79168-1 ◽

2008 ◽

Vol 2008 ◽

pp. 255-256

Author(s):

R.J. Arceci

Keyword(s):

Acute Myeloid Leukemia ◽

Children And Adolescents ◽

Myeloid Leukemia ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor ◽

Acute Myeloid

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Granulocyte Colony-Stimulating Factor (G-CSF) Treatment of Childhood Acute Myeloid Leukemias That Overexpress the Differentiation-Defective G-CSF Receptor Isoform IV Is Associated With a Higher Incidence of Relapse

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.9010 ◽

2010 ◽

Vol 28 (15) ◽

pp. 2591-2597 ◽

Cited By ~ 42

Author(s):

Stephanie Ehlers ◽

Christin Herbst ◽

Martin Zimmermann ◽

Nicole Scharn ◽

Manuela Germeshausen ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Children And Adolescents ◽

Cumulative Incidence ◽

Myeloid Leukemia ◽

Cell Surface Expression ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor ◽

Acute Myeloid ◽

Factor G

Purpose This prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed. Patients and Methods Of 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene. Results In patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% ± 13%) compared with 14 patients with low-level isoform IV expression (14% ± 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF–treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049). Conclusion Our results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapse.

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