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

inv(1)(q24q25) RCSD1/ABL2

Written2018-10Baptiste Gaillard
Laboratoire d'Hématologie 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

Keywords RCSD1, ABL2, B-cell acute lymphoblatic leukemia

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9819/3
Atlas_Id 1831

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 NameRCSD1
Location 1q24.2
Protein 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 NameABL2
Location 1q25.2
Protein 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

Hybrid gene
Description 5'RCSD1 (exon 3) - 3'ABL2 (exon 5).
  
Fusion Protein
 
  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).
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia.
Boer JM, Steeghs EM, Marchante JR, Boeree A, Beaudoin JJ, Beverloo HB, Kuiper RP, Escherich G, van der Velden VH, van der Schoot CE, de Groot-Kruseman HA, Pieters R, den Boer ML.
Oncotarget. 2017 Jan 17;8(3):4618-4628.
PMID 27855558
 
The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis.
Hempel A, Kühl SJ, Rothe M, Rao Tata P, Sirbu IO, Vainio SJ, Kühl M.
Dev Biol. 2017 Apr 1;424(1):28-39. doi: 10.1016/j.ydbio.2017.02.014. Epub 2017 Feb 22.
PMID 28237811
 
A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation.
Jacobsen FA, Scherer AN, Mouritsen J, Bragadóttir H, Thomas Bäckström B, Sardar S, Holmberg D, Koleske AJ, Andersson .
J Neuroimmune Pharmacol. 2018 Jun;13(2):265-276. doi: 10.1007/s11481-018-9783-8. Epub 2018 Mar 17.
PMID 29550892
 
ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling.
Kazi JU, Rupar K, Marhäll A, Moharram SA, Khanum F, Shah K, Gazi M, Nagaraj SR, Sun J, Chougule RA, Rönnstrand L.
Oncotarget. 2017 Feb 14;8(7):12194-12202. doi: 10.18632/oncotarget.14577.
PMID 28086240
 
RCSD1-ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia.
Raca G, Gurbuxani S, Zhang Z, Li Z, Sukhanova M, McNeer J, Stock W.
Leuk Lymphoma. 2015 Apr;56(4):1145-7.
PMID 25098428
 
Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL.
Roberts KG, Yang YL, Payne-Turner D, Lin W, Files JK, Dickerson K, Gu Z, Taunton J, Janke LJ, Chen T, Loh ML, Hunger SP, Mullighan CG.
Blood Adv. 2017 Aug 30;1(20):1657-1671.
PMID 29296813
 
Combinatorial proteomic analysis of intercellular signaling applied to the CD28 T-cell costimulatory receptor.
Tian R, Wang H, Gish GD, Petsalaki E, Pasculescu A, Shi Y, Mollenauer M, Bagshaw RD, Yosef N, Hunter T, Gingras AC, Weiss A, Pawson T.
Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):E1594-603. doi: 10.1073/pnas.1503286112. Epub 2015 Mar 17.
PMID 25829543
 

Citation

This paper should be referenced as such :
Gaillard B
t(1;1)(q24;q25) RCSD1/ABL2; inv(1)(q24q25) RCSD1/ABL2;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/inv1q24q25RCSD1ABL2ID1831.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(1;1)(q24;q25) RCSD1/ABL2

External links

Mitelman databaset(1;1)(q24;q25) [Case List]    t(1;1)(q24;q25) [Transloc-MCList] RCSD1/ABL2 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9819/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
REVIEW articlesautomatic search in PubMed
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