A recurrent immunophenotype at diagnosis independently identifies high-risk pediatric acute myeloid leukemia: a report from Children’s Oncology Group

Brodersen, Lisa Eidenschink; Alonzo, Todd A.; Menssen, Andrew J.; Gerbing, Robert B.; Pardo, Laura; Voigt, Andrew P.; Kahwash, Samir B.; Hirsch, Betsy A.; Raimondi, Susana C.; Gamis, Alan S.; Meshinchi, Soheil; Loken, Michael R.

doi:10.1038/leu.2016.119

Cited by 58 publications

(72 citation statements)

References 15 publications

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“…BMA/Bx revealed AML blasts with M0 (Figure ). Immunophenotyping demonstrated blasts that were CD45 dim , CD33 + , CD56 bright , and CD71 + CD117 + CD34 + , consistent with the RAM phenotype . Cytogenetics showed near triploidy with normal molecular testing (Table ).…”

Section: Descriptionmentioning

confidence: 87%

“…Previous reports of a single immunophenotype or multidimensional phenotypes as markers have failed to show prognostic significance . In the recent COG trial AAML0531, a recurrent, unique diagnostic immunophenotype of AML was identified in 2.3% pediatric patients with de novo AML . This immunophenotype was named RAM after the first patient in whom it was described.…”

Section: Discussionmentioning

confidence: 99%

“…Twin A received additional bortezomib during induction 1 which may have helped in achieving MRD‐negative status pre‐HCT. RAM AML has outcomes similar to other high‐risk AML; therefore, upfront intensified therapy and HCT which have been shown to abrogate poor outcomes in this patient population should be considered …”

Section: Discussionmentioning

confidence: 99%

“…Immunophenotype at diagnosis has not been used for stratification upfront. In the recent COG AML0531 study, nineteen patients with a distinctive multidimensional immunophenotype referred to as the RAM phenotype were identified . Although these patients were categorized standard risk, they had high rates of induction failure, relapse, and overall poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Abu‐Arja

Dargart

Bajwa

et al. 2018

Pediatric Transplantation

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AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.

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Section: Descriptionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Abu‐Arja

Dargart

Bajwa

et al. 2018

Pediatric Transplantation

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“…The CBFA2T3‐GLIS2 fusion oncogene is associated with a distinct immunophenotype characterized by overexpression of CD56 (NCAM1) and under‐expression of both HLA‐DR and CD38, similar to the one described as RAM phenotype (Eidenschink Brodersen et al , ). It has been demonstrated, through immunophenotypic analysis combined with morphological, genetic and clinical features, that the RAM phenotype (bright CD56 expression at minimum 2 log10 units greater than normal myeloid progenitors, dim‐to‐negative expression of CD45 and CD38, and lack of HLA‐DR) is a unique entity, distinct from CD56+ non‐RAM and CD56‐negative leukaemias.…”

Section: Immunophenotypic Characteristics Of Patients With the Cbfa2tmentioning

confidence: 94%

CBFA2T3‐GLIS2‐positive acute myeloid leukaemia. A peculiar paediatric entity

et al. 2018

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Summary The scenario of paediatric acute myeloid leukaemia (AML), particularly non‐Down syndrome acute megakaryoblastic leukaemia (non‐DS‐AMKL), has been recently revolutionized by the advent of large‐scale, genomic sequencing technologies. In this changing landscape, a significantly relevant discovery has been represented by the identification of the CBFA2T3‐GLIS2 fusion gene, which is the result of a cryptic inversion of chromosome 16. It is the most frequent chimeric oncogene identified to date in non‐DS‐AMKL, although it seems not to be exclusively restricted to the French‐American‐British M7 subgroup. The CBFA2T3‐GLIS2 fusion gene characterizes a subtype of leukaemia that is specific to paediatrics, having never been identified in adults. It characterizes an extremely aggressive leukaemia, as the presence of this fusion is associated with a grim outcome in almost all of the case series reported, with overall survival rates ranging between 15% and 30%. Although the molecular basis that underlies this leukaemia subtype is still far from being completely elucidated, unique functional properties induced by CBFA2T3‐GLIS2 in the leukaemogenesis driving process have been recently identified. We here review the peculiarities of CBFA2T3‐GLIS2‐positive AML, describing its intriguing clinical and biological behaviour and providing some challenging targeting opportunities.

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CD56, HLA‐DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3‐GLIS2 fusion transcript

et al. 2021

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The presence of CBFA2T3‐GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML‐CBFA2T3‐GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3‐GLIS2‐AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3‐GLIS2‐AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA‐DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak‐to‐negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA‐DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance.

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A recurrent immunophenotype at diagnosis independently identifies high-risk pediatric acute myeloid leukemia: a report from Children’s Oncology Group

Cited by 58 publications

References 15 publications

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

CBFA2T3‐GLIS2‐positive acute myeloid leukaemia. A peculiar paediatric entity

CD56, HLA‐DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3‐GLIS2 fusion transcript

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