t(1;1)(q24;q25) RCSD1/ABL2
inv(1)(q24q25) RCSD1/ABL2

2018-10-01   Baptiste Gaillard 

1.Laboratoire dHématologie CHU Reims, France; bgaillard@chu-reims.fr

Abstract

Review on t(1;1)(q24;q25)/inv(1)(q24q25), with data on clinics, and the genes involved

Clinics and Pathology

Disease

B-lymphoblastic leukemia, BCR-ABL1-like (WHO, 2016).

Epidemiology

Only 2 cases described: a 20-years-old man (Roberts et al, 2014; Raca et al., 2015; Roberts et al., 2017) and a second patient without further data (case A530 in Boer et al., 2017). These cases were first classified as B-ALL, and reclassified later as "B-ALL, BCR-ABL1-like" after characterization [CHU1]of the RCSD1/ABL2 fusion.
The RCSD1/ABL2 case described by Roberts et al, 2014 was part of a study of 1665 B-ALL cases, three of which with ABL2 fusions. In the case described in Boer et al., 2017, the RCDS1/ABL2 fusion case was identified in a series of 77 BCR-ABL1-like B-ALL cases.

Treatment

The 20-year-old case received induction therapy with vincristine/peg-asparaginase/daunorubicin/prednisone with intrathecal cytorabine and methotrexate; there was no response post induction at days 15 and 29). Additional therapy included Cytoxan, cytarabine, 6-mercaptopurine, decadron, vincristine, peg-asparaginase and intrathecal therapy with methotrexate (8-week cycle) and produced a morphologic remission but high-level minimal residual disease (MRD) was detected by flow cytometry. The patient received a hematopoietic stem cell transplant (total body irradiation and etoposide based preparative regimen) from an unrelated donor (Raca et al., 2015). The other case was treated according to the ALL10-HR protocol. There was a good response to prednisone, and high MRD (Boer et al., 2017).

Evolution

The 20-year-old case was in complete remission 8 month post-transplant and with no evidence of MRD (Raca et al., 2015). The other patient has been followed up for 3-4 years (Boer et al., 2017).

Prognosis

The two cases showed a IKZF1 deletion. Roberts et al. showed a tyrosine kinase inhibitors sensitivity when the RCSD1/ABL2 fusion was tested in Ba/F3 cells and in vivo mice models, and dasatinib was proposed to be evaluated in the future treatment of BCR-ABL1-like B-ALL with ABL-class fusions, especially for RCSD1/ABL2 fusion)(Roberts et al, 2017)

Cytogenetics

Cytogenetics morphological

This abnormality was not detected by conventional cytogenetic in any of the two cases. A complex rearrangement necessarily occurs because the two genes are in opposite directions of transcription.

Cytogenetics molecular

The rearrangement can be detected by molecular cytogenetics or other molecular technics.

Genes Involved and Proteins

Gene name
Location
1q24.2
Protein description
416 amino acids. RCSD1 is also called CAPZIP. CapZ-interacting protein, implication in cytoskeleton regulation and cell migration. RCSD1 is a mediator of non-canonical Wnt/JNK signalling. It interacts with the actin capping protein CapZ (CAPZA1, CAPZA2, CAPZB: capping actin protein of muscle Z-line subunits alpha 1, alpha 2 and beta). RCSD1 Binds CapZ to prevent CapZ from binding to the actin cytoskeleton. The T-cell costimulatory receptor CD28 phosphorylation regulates RCSD1 (Hempel et al. 2017: Tian et al. 2015).
Gene name
Location
1q25.2
Protein description
1182 amino acids. ABL2 is also called ARG. ABL2 is a member of the ABL family of tyrosine kinases. ABL kinases have been found to play essential roles for the downstream signaling of the T- and B-cell receptors. ABL1 and ABL2 have both overlapping and distinct functions. The two proteins diverge in their C-terminal halves: ABL2 contains two F-actin binding domains and a microtubule-binding domain and is a key regulator of actin cytoskeletal remodeling. ABL2 acts as negative regulator of signaling downstream of the kinase activity of the transmembrane receptor protein tyrosine kinase FLT3: it partially blocks FLT3-induced AKT phosphorylation (Jacobsen et al., 2018; Kazi et al., 2017). ABL2 gene is often implicated in solid tumors.

Result of the Chromosomal Anomaly

Description

5RCSD1 (exon 3) - 3ABL2 (exon 5).
Atlas Image
RCSD1/ABL2 fusion protein, according to https://pecan.stjude.cloud/proteinpaint/ABL2

Description

The transcript retains the tyrosine kinase domain of ABL2 and a portion of the SH2 domain, but not the NH2-terminal SH3 domain (Raca et al., 2015).

Highly cited references

Pubmed IDYearTitleCitations
292968132017Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL.46
278940772017Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia.26
278555582017Diagnostic evaluation of RNA sequencing for the detection of genetic abnormalities associated with Ph-like acute lymphoblastic leukemia (ALL).7
250984282015RCSD1-ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia.2

Bibliography

Pubmed IDLast YearTitleAuthors
278555582017Diagnostic evaluation of RNA sequencing for the detection of genetic abnormalities associated with Ph-like acute lymphoblastic leukemia (ALL).Yap KL et al
282378112017The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis.Hempel A et al
295508922018A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation.Jacobsen FA et al
280862402017ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling.Kazi JU et al
250984282015RCSD1-ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia.Raca G et al
292968132017Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL.Roberts KG et al
258295432015Combinatorial proteomic analysis of intercellular signaling applied to the CD28 T-cell costimulatory receptor.Tian R et al

Summary

Fusion gene

RCSD1/ABL2

Citation

Baptiste Gaillard

t(1;1)(q24;q25) RCSD1/ABL2
inv(1)(q24q25) RCSD1/ABL2

Atlas Genet Cytogenet Oncol Haematol. 2018-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1831/t(1;1)(q24;q25)

External Links