Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3)

Bhatnagar, Bhavana; Blachly, James S.; Kohlschmidt, Jessica; Eisfeld, Ann Kathrin; Volinia, Stefano; Nicolet, Deedra; Carroll, Andrew J.; Block, AnneMarie W.; Kolitz, Jonathan E.; Stone, Richard; Mrózek, Krzysztof; Byrd, John C.; Bloomfield, Clara D.

doi:10.1038/leu.2015.345

Cited by 12 publications

(12 citation statements)

References 13 publications

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“…Our preliminary results seem to support this approach for most CK-AML patients with rare recurrent balanced abnormalities, who either do not harbor any or have very few gene mutations in addition to their balanced chromosome abnormality, and infrequently carry TP53 mutations. This resembles findings of others 18,45 and ours 14,46 in patients with balanced rearrangements involving 11q23/ KMT2A ( MLL ), who have very few gene mutations. It is possible that once more cases with such currently rare recurrent balanced abnormalities as t(8;16)(p11.2;p13.3), t(12;22)(p13;q12) or t(10;11)(p13;q21), each present in one patient in our series, are reported in the literature, these chromosome abnormalities will be recognized by the WHO classification as denoting specific clinico-pathologic entities of AML.…”

Section: Discussionsupporting

confidence: 90%

Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically

et al. 2019

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Complex karyotype (CK) with ≥3 abnormalities is detected in 10-12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q and/or 17p chromosome arms. The presence of 5q, 7q and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well-characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients. They included 136 patients with ≥3 exclusively unbalanced chromosome abnormalities, 96 of whom had a typical CK and 40 atypical CK, and 24 patients with ≥1 balanced abnormality in addition to ≥2 unbalanced ones. Patients with atypical CK-AML differed from those with typical CK-AML: they carried TP53 mutations less often ( P <0.001) and more often PHF6 ( P =0.008), FLT3 -TKD ( P =0.02), MED12 ( P =0.02) and NPM1 ( P =0.02) mutations. They were younger ( P= 0.007), had higher WBC ( P =0.001) and percentages of marrow ( P <0.001) and blood ( P =0.006) blasts, higher complete remission rates ( P =0.02) and longer overall survival ( P <0.001), thus indicating that atypical and typical CK-AMLs constitute distinct disease subtypes. We also identified smaller patient subsets within both typical and atypical CK-AML that differed molecularly and clinically.

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Section: Discussionsupporting

confidence: 90%

Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically

et al. 2019

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“… 6 , 36 Specifically, there was a paucity of biallelic CEBPA mutations (1%) and NPM1 mutations (5%), whereas mutations in the RAS pathway (29%) and kinases (22%) functional groups were relatively frequent. As previously described, 39 , 40 AML patients with 11q23/ MLL -rearrangements often had mutations in RAS pathway genes, whereas they rarely harbored mutations in other functional groups compared with patients with non- MLL -rearranged balanced rearrangements. For example, only 9% of MLL- rearranged patients (subgroups #6–12) harbored mutations in chromatin remodeling genes vs 26% of patients with non- MLL -rearranged balanced rearrangements (subgroups #13–18), and similar differences were observed for tumor suppressor (3% vs 18%), methylation-related (12% vs 23%) and spliceosome (12% vs 24%) functional groups.…”

Section: Resultssupporting

confidence: 54%

The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia

et al. 2017

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Recurrent chromosomal abnormalities and gene mutations detected at the time of diagnosis of acute myeloid leukemia (AML) are associated with particular disease features, treatment response and survival of AML patients, and are used to denote specific disease entities in the World Health Organization classification of myeloid neoplasms and acute leukemia. However, large studies that integrate cytogenetic and comprehensive mutational information are scarce. We created a comprehensive oncoprint of mutations associated with recurrent cytogenetic findings by combining the information on mutational patterns of 80 cancer- and leukemia-associated genes with cytogenetic findings in 1603 adult patients with de novo AML. We show unique differences in the mutational profiles among major cytogenetic subsets, identify novel associations between recurrent cytogenetic abnormalities and both specific gene mutations and gene functional groups, and reveal differences in cytogenetic and mutational features between patients younger than 60 years and those aged 60 years or older. The identified associations between cytogenetic and molecular genetic data may help guide mutation testing in AML, and result in more focused application of targeted therapy in patients with de novo AML.

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“…The present study assessed two patients with t(11;19)(q23;p13) AML, patient 1 (M4) had no MLL rearrangement, while patient 2 (M2) had MLL/ELL rearrangement, and both presented with early relapse (less than half a year). Consistent with previous findings (12)(13)(14), the results of the present study demonstrated that t(11;19)(q23;p13) was associated with a poor prognosis and short OS time in patients with AML, and indicated that it is necessary for these patients to receive allo-HSCT in first CR.…”

Section: Discussionsupporting

confidence: 92%

Successful treatment of two relapsed patients with t(11;19)(q23;p13) acute myeloid leukemia by CLAE chemotherapy sequential with allogeneic hematopoietic stem cell transplantation: Case reports

et al. 2021

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The prognosis of patients with relapsed/refractory acute myeloid leukemia (R/R AML) is poor, with a 3-year overall survival rate of 10%. Patients with translocation (t)(11;19)(q23;p13) have a higher risk of relapse and there is no optimal regimen for these patients. The present study treated two young patients with t(11;19)(q23;p13) AML, who relapsed after one or two cycles of consolidation, with a salvage treatment consisting of sequential cladribine, cytarabine and etoposide (CLAE) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Both neutrophil and platelet engraftments were achieved within 15 days, and no severe transplant-related complications and graft-versus-host diseases were observed. Following allo-HSCT, both patients achieved complete hematologic and cytogenetic remission. Decitabine was used for the prophylaxis of relapse. The two patients remained alive and disease-free for 100 days following allo-HSCT. The results presented here suggest that CLAE regimen sequential with allo-HSCT may be effective in treating patients with R/R AML, with t(11;19)(q23;p13). However, further studies and a larger sample size are required to validate the effectiveness of this treatment regimen.

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Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3)

Cited by 12 publications

References 13 publications

Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically

Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically

The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia

Successful treatment of two relapsed patients with t(11;19)(q23;p13) acute myeloid leukemia by CLAE chemotherapy sequential with allogeneic hematopoietic stem cell transplantation: Case reports

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