Co-occurrence of CRLF2-rearranged and Ph+ acute lymphoblastic leukemia: a report of four patients

Jain, Nitin; Lu, Xinyan; Daver, Naval; Thakral, Beenu; Wang, Sa A.; Konoplev, Sergej; Patel, Keyur P.; Kanagal‐Shamanna, Rashmi; Valentine, Marcus B.; Tang, Guilin; Pemmaraju, Naveen; Jorgensen, Jeffrey L.; Kebriaei, Partow; Núñez, César; Wierda, William G.; Jabbour, Elias; Roberts, Kathryn G.; Mullighan, Charles G.; Kantarjian, Hagop M.; Konopleva, Marina

doi:10.3324/haematol.2016.161000

Cited by 16 publications

(17 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionsupporting

confidence: 71%

“…This scenario illustrates the fact that Ph-like ALL can occur in the context of other cytogenetic abnormalities and mutations, including high-risk alterations [1,2,4,6,22]. Indeed, the co-occurrence of BCR-ABL1 in association with CRLF2-rearrangement in the same leukemia clone was reported recently in a case-series similar to this scenario [22]. Ph+ ALL in adults is a high-risk leukemia, and allogeneic HCT consolidation is indicated in CR1, even in the era of TKI given the survival benefit that has been demonstrated in transplanted patients [23,24].…”

Section: Discussionmentioning

confidence: 86%

See 1 more Smart Citation

Adults with Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia: Considerations for Allogeneic Hematopoietic Cell Transplantation in First Complete Remission

Aldoss

Kamal

Forman

et al. 2019

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

A B S T R A C T Philadelphia chromosomeÀlike (Ph-like) acute lymphoblastic leukemia (ALL) is a subset of high-risk B cell ALLs. A large proportion of Ph-like ALL cases carry activating kinase mutations that could potentially allow them to be targeted by tyrosine kinase inhibitors. Ph-like ALL is not an uncommon entity, especially among adults, with a frequency exceeding 20%, including in older patients (>60 years old) with ALL. Ph-like ALL is associated with inferior outcomes across all ages, and studies have consistently shown a higher incidence of persistent postinduction minimal residual disease in patients carrying Ph-like ALL compared with other subgroups of ALL, and this translates into inferior leukemia-related outcomes. The inferior outcome of conventional chemotherapy for Ph-like ALL in adults raises the fundamental question of whether all adults with Ph-like ALL require an allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) regardless of other presenting features and treatment response parameters. Here we present and discuss several scenarios in which adults with Ph-like ALL underwent or were considered for HCT in CR1 for various reasons. Although the decision to proceed with HCT was clear and indisputable in some of these situations, in others we struggled with the decision to transplant in CR1 because of the lack of published data regarding the efficacy of allogeneic HCT as consolidation for Ph-like ALL. We emphasize the urgent need for developing well-designed studies to address this important question.

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 86%

Adults with Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia: Considerations for Allogeneic Hematopoietic Cell Transplantation in First Complete Remission

Aldoss

Kamal

Forman

et al. 2019

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…Moreover, though it has been suggested to represent a primary lesion 44 , iAMP21, in a minor proportion of patients, co-occurs with other primary aberrations such as BCR–ABL1 or ETV6–RUNX1 fusions. Similarly, CRLF2 rearrangement ( CRLF2 r) that is sometimes used to define the subset of patients within B-other ALL 45 is frequently a secondary aberration 46 and also occurs across several BCP-ALL subtypes ( BCR-ABL1 -positive ALL, BCR-ABL1 -like ALL, and hyperdiploid and hypodiploid ALL) 11 , 41 , 47 , 48 . Nevertheless, identification of these aberrations is clinically relevant, as some of them were proven to have unfavorable prognostic impact and thus influence risk stratification and therapy (for example, iAMP21 49 , 50 and TCF3–HLF 51 ) whereas in others the suggested prognostic impact needs further validation (for example, PAX5 amp 52 ).…”

Section: New Bcp-all Subtypesmentioning

confidence: 99%

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

2018

View full text Add to dashboard Cite

Traditionally, genetic abnormalities detected by conventional karyotyping, fluorescence in situ hybridization, and polymerase chain reaction divided childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) into well-established genetic subtypes. This genetic classification has been prognostically relevant and thus used for the risk stratification of therapy. Recently, the introduction of genome-wide approaches, including massive parallel sequencing methods (whole-genome, -exome, and -transcriptome sequencing), enabled extensive genomic studies which, together with gene expression profiling, largely expanded our understanding of leukemia pathogenesis and its heterogeneity. Novel BCP-ALL subtypes have been described. Exact identification of recurrent genetic alterations and their combinations facilitates more precise risk stratification of patients. Discovery of targetable lesions in subsets of patients enables the introduction of new treatment modalities into clinical practice and stimulates the transfer of modern methods from research laboratories to routine practice.

show abstract

“…Certain studies have confirmed that CRLF2 serves a key role in the development of B lymphocytes, and mutations in the CRLF2 gene may further activate the CRLF2/thymic stromal lymphopoietin (TSLP) signaling pathway and induce B-ALL (15–17). Moreover, CRLF2 is a marker for Ph-like ALL.…”

Section: Discussionmentioning

confidence: 99%

Potential efficacy and prognosis of silencing the CRLF2‑mediated AKT/mTOR pathway in pediatric acute B‑cell lymphoblastic leukemia

Jiang

Zou

2018

Oncol Rep

View full text Add to dashboard Cite

Acute B-cell lymphoblastic leukemia (B-ALL) is a common type of blood cancer, which is associated with aberrant gene expression. Cytokine receptor-like factor 2 (CRLF2) serves a crucial role in the growth and allergic and inflammatory responses of dendritic cells and T cells. The purpose of the present study was to investigate the potential therapeutic and prognostic effect of silencing the CRLF2-mediated RAC-α serine/threonine-protein kinase (AKT)/serine/threonine-protein kinase mTOR (mTOR) pathway in B-ALL. In our study, bone marrow specimens were collected from 128 children with B-ALL and 26 healthy children. The expression of CRLF2 in bone marrow tissue was detected using immunohistochemistry. The survival rates were compared among the children with high and low CRLF2 expression levels. BaF3 leukemia cells were treated with CRLF2 short hairpin RNA knockdown and/or the AKT/mTOR pathway specific inhibitor LY294002. mRNA and protein expression associated with CRLF2 and the AKT/mTOR pathway in each group was detected by reverse transcription-quantitative polymerase chain reaction analysis and western blotting. The viability of BaF3 cells in all the groups was assessed by Cell Counting Kit-8 assay; the migration and invasion of BaF3 cells were determined by wound healing and Transwell invasion assays; and the sensitivity of BaF3 cells to the chemotherapeutic drug imatinib was detected using flow cytometry. The results demonstrated that CRLF2 overexpression is associated with a poor prognosis in B-ALL, and the CRLF2/AKT/mTOR pathway is involved in the migration, invasion and chemotherapeutic agent-induced apoptosis of BaF3 cells.

show abstract

Co-occurrence of CRLF2-rearranged and Ph+ acute lymphoblastic leukemia: a report of four patients

Cited by 16 publications

References 18 publications

Adults with Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia: Considerations for Allogeneic Hematopoietic Cell Transplantation in First Complete Remission

Adults with Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia: Considerations for Allogeneic Hematopoietic Cell Transplantation in First Complete Remission

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

Potential efficacy and prognosis of silencing the CRLF2‑mediated AKT/mTOR pathway in pediatric acute B‑cell lymphoblastic leukemia

Contact Info

Product

Resources

About