Acute myeloid leukemia with inv(16) with CBFB–MYH11, 3′CBFB deletion, variant t(9;22) with BCR–ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review

Tirado, Carlos A; Valdez, Federico; Klesse, Laura J.; Karandikar, Nitin J.; Uddin, Naseem; Arbini, Arnaldo; Fustino, Nicholas J.; Collins, Robert H.; Patel, Sangeeta; Smart, Ruth L.; Garcia, Rolando; Doolittle, Jeff; Chen, Weina

doi:10.1016/j.cancergencyto.2010.03.001

Cited by 23 publications

(16 citation statements)

References 12 publications

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“…BCR-ABL1 has been described in AML together with different class II aberrations such as CBFB-MYH11, RUNX1-RUNX1T1, PML-RARA, and NPM1 [1,11,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Section: Molecular Pathogenesis and Phenotypementioning

confidence: 99%

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

et al. 2016

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BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease. Our analysis shows that BCR-ABL predominantly occurs in AML-NOS, CBF leukemia, and AML with myelodysplasia-related changes. The most common BCR-ABL transcripts (p190 and p210) are nearly equally distributed. Based on the analysis of published data, we provide a clinical algorithm for the initial differential diagnosis of BCR-ABL+ AML. The prognosis of BCR-ABL+ AML seems to depend on the cytogenetic and/or molecular background rather than on BCR-ABL itself. A therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib is reasonable, but-due to a lack of systematic clinical data-their use cannot be routinely recommended in first-line therapy. Beyond first-line treatment of AML, the use of TKI remains an individual decision, both in combination with intensive chemotherapy and/or as a bridge to allogeneic stem cell transplantation. In each single case, potential benefits have to be weighed against potential risks.

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Section: Molecular Pathogenesis and Phenotypementioning

confidence: 99%

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

et al. 2016

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“…From a molecular standpoint, the inversion of chromosome 16 creates the pathologic fusion gene CBFB/MYH11 , which reportedly alters transcriptional regulation [2]. The BCR/ABL1 rearrangement, created by t(9;22)(q34;q11.2), is characteristic of chronic myelogenous leukemia (CML) but also occurs in precursor lymphoid neoplasm and AML [3]. Coexistence of the t(9;22) and inv(16) chromosomal aberrations is a rare occurrence that has been described in CML (mainly the myeloid blast phase [CML-BP]), de novo AML, and a few cases of therapy-related AML (t-AML) [2, 3, 4, 5, 6].…”

Section: Introductionmentioning

confidence: 99%

“…The BCR/ABL1 rearrangement, created by t(9;22)(q34;q11.2), is characteristic of chronic myelogenous leukemia (CML) but also occurs in precursor lymphoid neoplasm and AML [3]. Coexistence of the t(9;22) and inv(16) chromosomal aberrations is a rare occurrence that has been described in CML (mainly the myeloid blast phase [CML-BP]), de novo AML, and a few cases of therapy-related AML (t-AML) [2, 3, 4, 5, 6]. Most of the de novo forms of AML with the t(9;22) and inv(16) chromosomal abnormalities have a favorable prognosis comparable to that of AML with inv(16) alone [6].…”

Section: Introductionmentioning

confidence: 99%

Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities

et al. 2014

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BackgroundThe coexistence of t(9;22)(q34;q11.2) and inv(16)(p13q22) chromosomal abnormalities is extremely uncommon, and only a small number of such cases have been reported. Here, we characterized 7 cases of hematologic malignancy exhibiting t(9;22) and inv(16) coexistence.MethodsWe reviewed the cytogenetic data for hematologic malignancies treated at the Catholic Blood and Marrow Transplantation Center between January 2004 and June 2013. We identified 7 cases exhibiting t(9;22) and inv(16) coexistence. In addition, we analyzed mutations in the IKZF1, NPM1, FLT3, N-RAS, K-RAS, c-KIT, and TP53 genes.ResultsFour cases of chronic myelogenous leukemia (CML; 1 chronic phase, 2 accelerated phase, and 1 blast phase) and 3 cases of acute myeloid leukemia (AML; 1 de novo and 2 therapy-related) were identified. The percentages of circulating blasts and bone marrow eosinophils were higher in AML cases than in CML cases (53% vs. 5% and 30% vs. 5.5%, respectively). The proportions of each chromosomal abnormality were used along with follow-up karyotyping results to identify secondary changes. In BCR/ABL, a p210 fusion transcript was associated with CML, whereas a p190 fusion transcript was associated with AML. One patient with AML harbored 2 mutations: c-KIT D816V and TP53 E11Q. All patients except 1 with CML blast phase sustained clinical remission after treatment, which included an imatinib mesylate regimen.ConclusionThis study shows that observations of bone marrow morphology, initial and follow-up cytogenetic studies, and karyotyping of BCR/ABL1 and CBFB/MYH11 provide valuable information for characterizing hematologic malignancies exhibiting t(9;22) and inv(16) coexistence.

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“…44 Evidence for this hypothesis was obtained by comparing gene expression profiles of monosomy 7 and focal IKZF1 deletions. We found a statistically significant correlation on non-chromosome 7 genes.…”

Section: T O R T I F O U N D a T I O Nmentioning

confidence: 99%

Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o nby controlling transcriptional regulators, such as GATA1 and RUNX1. 18,20 Although IKZF1 is not required for the initial differentiation towards granulocytes and monocytes, IKZF1 represses differentiation of the basophilic granulocyte lineage and promotes early maturation and survival of the neutrophil granulocyte lineage. 17,21,22 In pediatric AML, monosomy 7 is found in only 4%-5% of patients. The 5-year OS and EFS of pediatric AML patients with monosomy 7 with or without additional cytogenetic or chromosomal aberrations are poor. 23 In adult AML, monosomy 7 is the most frequent single monosomy and has a similar poor 4-year OS as compared to other single autosomal monosomies. 24 Deletions of the short arm of chromosome 7, 7p (del7p) were recurrently found in adult de novo AML and secondary AML developed from myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). [25][26][27] Furthermore, 7p deletions were mapped to the IKZF1 locus and it was shown that loss of IKZF1 is acquired during the progression of MPN to secondairy AML, indicating that loss of IKZF1 contributes to the transformation from MPN to AML. 25 Together, these studies demonstrate that IKZF1 may play a role in myeloid differentiation and that loss of IKZF1 may contribute to myeloid oncogenesis. We, therefore, hypothesized that, in pediatric AML patients with monosomy 7, IKZF1 may be an important player. In this study, we analyzed the frequency of IKZF1 deletions in a pediatric AML cohort, and studied the difference in gene expression of cases with focal IKZF1 deletions, and cases with monosomy 7. Methods Patients' samplesSamples were provided by the Dutch Childhood Oncology Group (DCOG, the Netherlands), the AML-Berliner-FrankfurtMünster Study Group (Germany and Czech Republic), the SaintLouis Hospital (France), and the Royal Hospital for Sick Children (UK). Isolation of genomic DNA and total cellular RNA was performed using Trizol reagent. Each study group provided morphological and cytogenetic classification and clinical data. Institutional review board approval for these studies had been obtained in the participating centers. Detection of deletions and mutations of IKZF1Multiplex ligation-dependent probe amplification (MLPA) was performed using the p335-B1;ALL-IKZF1 kit (MRC Holland, Amsterdam, the Netherlands; data available at http: //www.mlpa.com). The data were analyzed with GeneMarker v. 1.85 (SoftGenetics, State College, Pennsylvania, USA). Data were normalized to reference probes and control samples. A deletion was defined as a peak ratio below 0.75; an amplification was defined as a peak ratio above 1.25.Array comparative genomic hybridization (Array-CGH) was performed using the human genome CGH Microarray 105K (Agilent Technologies, Santa Clara, California, USA) according to the manufacturer's protocol; data were analyzed with Genomic Workbench v. 5.0.14 (Agilent Technologies, Santa Clara, California, USA).Direct sequencing was used to analyze mutations or frameshif...

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Acute myeloid leukemia with inv(16) with CBFB–MYH11, 3′CBFB deletion, variant t(9;22) with BCR–ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review

Cited by 23 publications

References 12 publications

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities

Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

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