Disease |
B-cell precursor ALL with expression of CD79a+, CD19+, CD10+, TdT (Mustjoki et al., 2009; Collette et al., 2015 ) |
Epidemiology | 12 cases with an ABL1 split by FISH and/or RCSD1/ABL1 fusion, aged 5 to 40 years (median age 15 years); male predominance (8 males and 4 females); among them 1 with ABL1-positive biphenotypic ALL in which, however, the partner gene has not been identifed. |
Cytology | Hyperleukocytosis (WBC range at diagnosis 24 to 470 x 109, median 110 x 109); bone marrow blasts ranging from 58 to 95%. |
Prognosis | Poor response to induction chemotherapy and in addition to induction failure, a high risk of relapse including patients after bone marrow transplantation. B-ALL patients with the RCSD1/ABL1 fusion are characterized by susceptibility to tyrosine kinase inhibitor therapy (imatinib, dasatinib, ponatinib) and may achieve transient clinical effects as well as long time remission (Table 1; Data from De Braekeleer et al., 2013; Perwein et al., 2016) | Sex/ Age | Diagnosis | WBC (x109/L) | PB/BM blasts (%) | Genetic testing results | Therapy | Survival (months) | 1 | M/15 | BAL | 122 | 95/ NA | 46,XY,t(1;9)(q23.3~q25;q34) ABL1-rearranged (FISH) | Chemotherapy | 10 died | 2* | M/11 | B-ALL | 6 | 47/92 | 46,Y,add(X)(p22),t(1;9)(q24;q34) ABL1-rearranged (FISH) RCSD1-ABL1 | Chemotherapy, BMT, relapsed 2 years after the initial treatment | 97 | 3 | 40/M | B-ALL | 24 | 34/80 | 46,XY,t(1;9)(q24;q34) RCSD1-ABL1 | Chemotherapy + dasatinib, BMT Chemotherapy + dasatinib/ imatinib at relapse | 66 | 4 | F/18 | B-ALL | 110 | 87/ 92 | t(1;9)(q24;q34) ABL1-rearranged (FISH) RCSD1-ABL1 | NA | NA | 5 | F/15 | B-ALL | 348 | NA/NA | 46,XX,t(1;9)(q24;q34) RCSD1-ABL1 | Chemotherapy, BMT at 4, 35 and 84 months following relapse. | 84 died | 6 | M/31 | B-ALL | 146 | 90/NA | 46,XY,t(1;9)(q23;q34),inv(2)(p21q33) Developed: 45,XY,t(1;9),inv(2),t(5;16)(q33;q24), dic(18;20)(p11;q11) and 46,XY,t(1;9),inv(2),t(5;16),dic(18;20),der(19)t(17;19)(q21;p13),+21 RCSD1-ABL1 | Chemotherapy, transient clinical effects with imatinib, and dasatinib. | 6.5 died | 7 | M/16 | B-ALL | 48 | NA/ NA | RCSD1-ABL1 identified by RNA-sequence analysis | NA | NA | 8 | M/18 | B-ALL | 470 | 52/58 | 46,XY,t(1;9)(q24;q34) RCSD1-ABL1 | No compliance to therapy | 12+ | 9 | M/6 | B-ALL | 108 | NA/ NA | 46,XY,t(1;9)(q23;q34) ABL1-rearranged RCSD1-ABL1 | Chemotherapy + imatinib, poor response to chemotherapy | 1 | 10 | F/26 | B-ALL | 26 | 84/86 | 46,XX,t(1;9)(q24;q34) RCSD1-ABL1 | Chemotherapy +dasatinib, BMT, relapse Chemotherapy +ponatinib, BMT Ponatinib monotherapy, relapse | 25 died | 11 | F/15 | B-ALL | 251 | 45/NA | 46,XX,t(1;9)(q24;q34) IKS deletion | Chemotherapy + dasatinib BMT | 8 died | 12 | M/15 | B-ALL | 69 | 71/95 | 46,XY,t(1;9)(q31?;q34) RCSD1-ABL1 | Chemotherapy + imatinib 2 months after relapse: sustained clinical remission | 163 |
Abbreviations: WBC., white blood cells; PB., peripheral blood; BM., bone marrow; M., male; F., female; ALL., acute lymphocytic leukemia; * at relapse; BMT., bone marrow transplantation. 1. Gonzales et al., 2004; 2. De Braekeleer et al., 2011; 3. Mustjoki et al., 2009; 4. Zamecnikova et al., 2010; De Braekeleer et al., 2013; 5. De Braekeleer et al., 2011; 6. Inokuchi et al., 2011; 7. Roberts et al., 2012; 8. De Braekeleer et al., 2013; 9. Roberts et al., 2014; 10. Collette et al.,2015; 11. Kamran et al., 2015; 12. Perwein et al., 2016. |
Drug response profiling can predict response to ponatinib in a patient with t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia |
Collette Y, Prébet T, Goubard A, Adélaïde J, Castellano R, Carbuccia N, Garnier S, Guille A, Arnoulet C, Charbonier A, Mozziconacci MJ, Birnbaum D, Chaffanet M, Vey N |
Blood Cancer J 2015 Mar 13;5:e292 |
PMID 25768406 |
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Acute lymphoblastic leukemia associated with RCSD1-ABL1 novel fusion gene has a distinct gene expression profile from BCR-ABL1 fusion |
De Braekeleer E, Douet-Guilbert N, Guardiola P, Rowe D, Mustjoki S, Zamecnikova A, Al Bahar S, Jaramillo G, Berthou C, Bown N, Porkka K, Ochoa C, De Braekeleer M |
Leukemia 2013 Jun;27(6):1422-4 |
PMID 23168614 |
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The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ. |
Eyers CE, McNeill H, Knebel A, Morrice N, Arthur SJ, Cuenda A, Cohen P |
The Biochemical journal. 2005 ; 389 (Pt 1) : 127-135. |
PMID 15850461 |
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A t(1;9)(q23 |
González García JR, Bohlander SK, Gutiérrez Angulo M, Esparza Flores MA, Picos Cárdenas VJ, Meza Espinoza JP, Ayala Madrigal Mde L, Rivera H |
3 approximately q25;q34) affecting the ABL1 gene in a biphenotypic leukemia Cancer Genet Cytogenet |
PMID 15193448 |
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RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal translocations |
Inokuchi K, Wakita S, Hirakawa T, Tamai H, Yokose N, Yamaguchi H, Dan K |
Int J Hematol 2011 Sep;94(3):255-60 |
PMID 21863287 |
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RCSD1-ABL1 Translocation Associated with IKZF1 Gene Deletion in B-Cell Acute Lymphoblastic Leukemia |
Kamran S, Raca G, Nazir K |
Case Rep Hematol 2015;2015:353247 |
PMID 26600955 |
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A novel dasatinib-sensitive RCSD1-ABL1 fusion transcript in chemotherapy-refractory adult pre-B lymphoblastic leukemia with t(1;9)(q24;q34) |
Mustjoki S, Hernesniemi S, Rauhala A, Kähkönen M, Almqvist A, Lundán T, Porkka K |
Haematologica 2009 Oct;94(10):1469-71 |
PMID 19794096 |
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Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia |
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J, Mullighan CG |
N Engl J Med 2014 Sep 11;371(11):1005-15 |
PMID 25207766 |
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Chromosomal translocation t(1;9)(q24;q34) in acute lymphoblastic leukemia patient involving the ABL1 gene |
Zámecníkova A |
Leuk Res 2011 Sep;35(9):e149-50 |
PMID 21641035 |
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