Detection of ETV6 and RUNX1 gene rearrangements using fluorescence in situ hybridization in Mexican patients with acute lymphoblastic leukemia: experience at a single institution

Pérez-Vera, Patricia; Montero-Ruíz, Oreth; Frı́as, Sara; Ulloa-Avilés, V.; Cárdenas-Cardós, Rocío; Paredes‐Aguilera, Rogelio; Rivera-Luna, Roberto; Carnevale, Alessandra

doi:10.1016/j.cancergencyto.2005.03.018

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…In contrast to that reported for developed countries and for other hospital case studies in Mexico City [19][20][21][22], the genetic rearrangement most frequently found in this group of patients was MLL/AF4, a rearrangement associated with a poor prognosis of the disease [5,9]. In fact, five of the six children who died during the study period were carriers of MLL/ AF4.…”

Section: Discussioncontrasting

confidence: 74%

“…Before the current study, the lack of agreement between the frequency of TEL-AML1 found for Mexico City and that reported in the literature could have been due to an underestimation. In the majority of the analyses, the frequency of the MLL/AF4 rearrangement [19][20][21] was not evaluated. In one study [22] in which it was evaluated, the technique used was fluorescent in situ hybridization (FISH), which has been shown to lack the degree of sensitivity needed to detect these types of rearrangements [16,67,68]; in the study previously performed in the Mexican population, it could not be identified whether the type of genetic rearrangement associated with MLL was AF4 [22].…”

Section: Discussionmentioning

confidence: 99%

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Genetic rearrangementMLL/AF4is most frequent in children with acute lymphoblastic leukemias in Mexico City

Daniel-Cravioto

González-Bonilla

Mejı́a-Aranguré

et al. 2009

Leukemia & Lymphoma

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One of the highest incidences of acute lymphoblastic leukemia (ALL) in the world has been reported in Mexico City. In the current study (26 cases), the frequencies of the most frequent genetic rearrangements TEL-AML1, MLL/AF4, BCR-ABL (major and minor) in ALL in children from Mexico City were determined. For the ALL, the frequency of MLL/AF4 was 65.4%, for TEL-AML1 and that of BCR/ABL was 3.8%. Only 6 of the 17 children with the MLL/AF4 rearrangement were less than 26 months old. The frequency reported for MLL/AF4 in Mexican children with ALL is one of the highest worldwide. These findings could potentially explain the higher frequency of ALL with poor prognosis for children in Mexico City.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Genetic rearrangementMLL/AF4is most frequent in children with acute lymphoblastic leukemias in Mexico City

Daniel-Cravioto

González-Bonilla

Mejı́a-Aranguré

et al. 2009

Leukemia & Lymphoma

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“…The frequency of ETV6/RUNX1 in pediatric age group (1-15 years) of BCP-ALL was 18% (76/426). The median age group of ETV6/RUNX1-positive cases was 5, with peak distribution in age group 3-7 years (Figure 1), which is a narrower range than 2-10 years of peak incidence as reported in literature [4,16,17,36,37]. The frequency of ETV6/RUNX1-positive interphase cells in active disease was 40-100%.…”

Section: Etv6/runx1 and Clinico-hematopathological Correlationsmentioning

confidence: 76%

“…The incidence of ETV6/RUNX1 positivity (18%) in our series falls in the universal range of 15-30% [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] (Table 1). Our published data on recurrent translocations such as MLL, t(9;22) and t (1;19) in ALL also showed frequencies similar to the reported series from other countries [35,39].…”

Section: Etv6/runx1 and Hemato-pathological Correlationsmentioning

confidence: 96%

“…The t(12;21)(p13;q22) involving the ETV6 and the RUNX1 gene (ETV6/RUNX1, previously known as TEL/AML1), is the most frequent genetic abnormality in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), with a frequency ranging from 15 to 30% [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. It is a cryptic translocation invisible by conventional cytogenetic technique but can be detected by more sensitive techniques like fluorescence in situ hybridization (FISH) and RT-PCR.…”

Section: Introductionmentioning

confidence: 99%

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RUNX1 ABERRATIONS IN ETV6/RUNX1-POSITIVE AND ETV6/RUNX1-NEGATIVE PATIENTS: Its Hemato-Pathological and Prognostic Significance in a Large Cohort (619 Cases) of ALL

Pais

Kadam

Raje

et al. 2008

Pediatric Hematology and Oncology

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A large-cohort study (619) of acute lymphoblastic leukemia (ALL) revealed an ETV6/RUNX1 (previously known as TEL/AML1) incidence of 18% in pediatric B-cell precussor ALL, indicating no geographical heterogeinity. Association of CD34-negative phenotype, peak incidence in the 3- to 7-year age group, and a comparatively low frequency of ETV6 homologue loss in ETV6/RUNX1-positive cases were distinct findings in this series. Additional genetic changes, such as ETV6 loss, extra RUNX1, ETV6/RUNX1 duplication, and MLL aberrations in the ETV6/RUNX1-positive group, supported the hypothesis of the ETV6/RUNX1 leukemogenic model that these secondary changes are necessary for leukemogenesis rather than progression of disease. This study disclosed RUNX1 alterations in the ETV6/RUNX1-negative group of BCP-ALL that encourages the investigation of RUNX1 at a large scale with longer follow-up, which will focus on the prognostic importance and the underlying biology of disease.

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CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways

Lorenzana

León

et al. 2021

The Journal of Pathology CR

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The gene fusions BCR‐ABL1, TCF3‐PBX1, and ETV6‐RUNX1 are recurrent in B‐cell acute lymphoblastic leukemia (B‐ALL) and are found with low frequency in coexistence with CRLF2 (cytokine receptor‐like factor 2) rearrangements and overexpression. There is limited information regarding the CRLF2 abnormalities and dominant‐negative IKZF1 isoforms associated with surrogate markers of Jak2, ABL, and Ras signaling pathways. To assess this, we evaluated 24 Mexican children with B‐ALL positive for recurrent gene fusions at diagnosis. We found CRLF2 rearrangements and/or overexpression, dominant‐negative IKZF1 isoforms, and surrogate phosphorylated markers of signaling pathways coexisting with recurrent gene fusions. All the BCR‐ABL1 patients expressed CRLF2 and were positive for pCrkl (ABL); most of them were also positive for pStat5 (Jak2/Stat5) and negative for pErk (Ras). TCF3‐PBX1 patients with CRLF2 abnormalities were positive for pStat5, most of them were also positive for pCrkl, and two patients were also positive for pErk. One patient with ETV6‐RUNX1 and intracellular CRLF2 protein expressed pCrkl. In some cases, the activated signaling pathways were reverted in vitro by specific inhibitors. We further analyzed a TCF3‐PBX1 patient at relapse, identifying a clone with the recurrent gene fusion, P2RY8‐CRLF2, rearrangement, and phosphorylation of the three surrogate markers that we studied. These results agree with the previous reports regarding resistance to treatment observed in patients with recurrent gene fusions and coexisting CRLF2 gene abnormalities. A marker phosphorylation signature was identified in BCR‐ABL1 and TCF3‐PBX1 patients. To obtain useful information for the assessment of treatment in B‐ALL patients with recurrent gene fusions, we suggest that they should be evaluated at diagnosis for CRLF2 gene abnormalities and dominant‐negative IKZF1 isoforms, in addition to the analyses of activation and inhibition of signaling pathways.

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Detection of ETV6 and RUNX1 gene rearrangements using fluorescence in situ hybridization in Mexican patients with acute lymphoblastic leukemia: experience at a single institution

Cited by 15 publications

References 17 publications

Genetic rearrangementMLL/AF4is most frequent in children with acute lymphoblastic leukemias in Mexico City

Genetic rearrangementMLL/AF4is most frequent in children with acute lymphoblastic leukemias in Mexico City

RUNX1 ABERRATIONS IN ETV6/RUNX1-POSITIVE AND ETV6/RUNX1-NEGATIVE PATIENTS: Its Hemato-Pathological and Prognostic Significance in a Large Cohort (619 Cases) of ALL

CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways

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