Disease |
Myeloproliferative disorders (MPD) with eosinophilia (or chronic eosinophilic leukemia (CEL) and sporadic cases with acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (ALL) or lymphoma. |
Phenotype / cell stem origin |
Phenotypically diverse myeloid neoplasms that include patients that have been categorized as: chronic eosinophilic leukemia (CEL)/ atypical chronic myeloid leukemia with eosinophilia in 4 (Luciano et al., 1999; Rosati et al., 2006, Baxter et al., 2003, Li et al., 2011), chronic myeloproliferative disorder (MPD) in 2 (Darbyshire et al., 1987; Baxter et al., 2003), juvenile myelomonocytic leukemia (JMML) in 2, 1 of them congenital JMML (Grainger et al., 2002 Abraham et al., 2010), chronic myeloid leukemia (CML) in 1 (Hild & Fonatsch.,1990), myelodysplastic/myeloproliferative disease in 1 (Wilkinson et al., 2003), refractory anemia with excess of blasts in 1 (RAEB) (Xu et al., 2010) and acute myeloid leukemia in 3 (Baxter et al., 2003; Kern et al., 2002; Shearer et al., 2010). The remaining cases were lymphoid malignancies: 5 B-cell ALL (Craig et al., 1990; Barriga et al., 1996; Coyaud et al., 2010; Safavi et al., 2015), 1 mantle cell lymphoma (MCL) (Le Baccon et al., 2001) and 1 diffuse large B-cell lymphoma (DLBCL) (Le Baccon et al., 2001). |
Epidemiology | Male prevalence (12 males and 7 females) aged 0 to 79 years (median age 21 years) and notably, 5 patients were infants (1 male and 3 females) (Darbyshire et al., 1987; Wilkinson et al., 2003; Grainger et al., 2002; Abraham et al., 2010) (Table 1). Because the phenotypes are different, it may be that genes involved in this/these disease(s) are not similar; PDE4DIP and PDFRGB were found involved in MPD with eosinophilia (see below). Ref | Genes | Sex/age | Disease | Karyotype | Survival | 1 | PDE4DIP/PDGFRB | F/0 | MPD | 46,XX,t(1;5)(q23;q33) | 19+ months, on imatinib | 2 | TPM3/PDGFRB | M/21 | CES | 46,XY,t(1;5)(q21;q33) | Therapy with interferon and imatinib, alive 10+ years | 3 | TPM3/PDGFRB | M/8 | CEL | t(1;5)(q21;q33) | JMML from 1 year old; complete remission on imatinib, alive 8+ years? | 4 | PDGFRB rearranged | M | aCML/CEL | t(1;5)(q21;q33) | | 5 | PDGFRB rearranged | M | MPD | t(1;5)(q22;q31) | | 6 | PDGFRB rearranged | M/0 | JMML | t(1;5)(q21;q33) | 16+ months, on imatinib | 7 | No PDGFRB rearrangement | M | MDS/AML | t(1;5)(q21;q31) | | 8 | ? | F/31 | CML | 46,XX,add(1)(q?),t(9;22)(q34;q11) --> 46,XX,dup(1)(q23q32),t(9;22)/46,XX,t(1;5)(q21-22;q31),t(9;22) | | 9 | ? | F/0 | JMML | 46,XX,t(1;5)(q21;q33) | Alive after BMT 10+ years | 10 | ? | M | AML | 46,XY,t(8;21)(q22;q22) --> 46,XY,t(1;5)(q21;q33),t(8;21)/46,idem,del(11)(p13) | | 11 | ? | M/70 | AML | 45,XY,-7/46,idem,+21) --> 46-47,XY,inv(3)(q21q26),-7,+21,+mar/45,XY,inv(3),-7/45,XY,t(1;5)(q21;q31),inv(3),-7 RPN1/MECOM | | 12 | ? | M/51 | B-ALL | 46,XY,t(1;5)(q21;q31),del(9)(p12) | | 13 | ? | F/22 | B-ALL | 46,XX,t(1;5)(q21;q32)/42-48,idem,+8/48,idem,+der(5)t(1;5),+21 | | 14 | ? | F/67 | DLBCL (LN) | 51,XX,add(1)(p12),t(1;5)(q21;q31),der(2)dup(2)(p16p25)t(1;2) (q21;q31),der(3)t(1;3)(p21;q22),der(4)t(4;11)(q35;q13),del(6)(p21),+del(7)(?q22?q34),del(8)(q24),add(11)(p12),+12,+21,+2mar | | 15 | ? | F/0 | MPD | 46,XX,t(1;5)(q23;q33) | died 9 month after diagnosis | 16 | ? | M/0 | MPD | 46,XY,t(1;5)(q23;q33) | Alive 14+ months | 17 | ? | M/21 | CEL | 46,XY,t(1;5)(q23;q31) | interferon therapy, alive 7+ years | 18 | ? | F/79 | RAEB | 44,XX,t(1;5)(q23;q33),-7,der(12)t(7;12)(q?;p?)t(7;19)(q?;?),-18,der(19)t(11;19)(?;p11) | | 19 | ? | M/13 | B-ALL | 46,XY,t(1;5)(q23;q33) | Relapse after 3 months; CNS relapse on day + 106 after BMT and died. |
Abbreviations: M, male; F, female; MPD, Myeloproliferative disorder; CES; Chronic eosinophilic syndrome; CEL; Chronic eosinophilic leukemia; aCML, Atypical chronic myeloid leukemia; JMML, Juvenile myelomonocytic leukemia; MDS, myelodyslastic syndrome; AML; Acute myeloid leukemia; CML, Chronic myeloid leukemia; BMT, bone marrow transplantation; B-ALL, B-cell Acute lymphoblastic leukemia; DLBCL, Diffuse large B-cell lymphoma; LN, lymph node;, RAEB, Refractory anemia with excess of blasts. 1. Wilkinson et al., 2003; 2. Rosati et al., 2006; 3. Li et al., 2011; 4-5,7. Baxter et al., 2003; 6. Abraham et al., 2010; 8. Hild & Fonatsch.,1990; 9. Grainger et al., 2002; 10. Kern et al., 2002; 11. Shearer et al., 2010; 12. Coyaud et al., 2010; 13. Safavi et al., 2015;14. Le Baccon et al., 2001; 15-16. Darbyshire et al., 1987; 17. Luciano et al., 1999; 18. Xu et al., 2010; 19. Barriga et al., 1996. |
Clinics | Patients typically present with myeloproliferative neoplasm with eosinophilia and a spectrum of morphologic presentations. Although eosinophilia is characteristic of myeloid neoplasms associated with PDGFRB rearrangement, marked eosinophilia is not an invariable feature and the clinical presentation is variable. Patients are typically male and while children are rarely affected with PDGFRB gene fusions, 6 out of 19 described patients with t(1;5)(q21-23;q31-33) were children aged 0 to 13 years. |
Prognosis | One of the infants with MPD died 9 month after diagnosis and the other remains well on therapy 14 months from diagnosis (Darbyshire et al., 1987). The infant with PDE4DIP/PDGFRB fusion had refractory and progressive disease, but after therapy with imatinib was started complete clinical and hematologic remission, as well as major cytogenetic response was achieved (Wilkinson et al., 2003). 1 infant with JMML received autologous stem cell transplantation after initial cytoreductive therapy failed to control the disease and is alive at 10 years in full cytogenetic remission (Grainger et al., 2002) and 1 with congenital JMML is alive 16+ months on imatinib therapy (Abraham et al., 2010). The 8-year-old male with CEL and TPM3/PDGFRB fusion had rapid hematologic response and reduction of TPM3/PDGFRB transcripts after targeted therapy with imatinib (Li et al., 2011). The 21-years old patient with CEL obtained complete hematologic and major cytogenetic response after two years of interferon therapy and is alive 7 years from diagnosis (Luciano et al., 1999). The other 21- years old male with CEL and confirmed TPM3/PDGFRB fusion received interferon therapy for 10 years resulting in major cytogenetic response and after continuing with imatinib he achieved hematological, cytogenetic and FISH remission (Rosati et al., 2006). The 13-years-old boy with high-risk early pre-B ALL underwent allogeneic bone marrow transplantation after relapse but after a short second remission he had a central nervous system relapse and died (Barriga et al., 1996). From these data, it appears that patients with t(1;5)(q21-23;q31-33) and PDGFRB rearrangement have imatinib-responsive disease with durable remissions. |
Myeloid Neoplasm with PDGFRB Translocation, t(1;5)(q21;q33): A Congenital Presentation of An Imatinib Responsive Congenital JMML with Eosinophilia. |
Abraham SM, Salama ME, Jacobsen JR, Hancock J, Fluchel M. |
Blood 2010; 116:4092. |
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t(1;5)(q23;q33) in a patient with high-risk B-lineage acute lymphoblastic leukemia |
Barriga F, Bertin P, Legües E, Risueño C, Andrade W, Cabrera E, Grebe G |
Cancer Genet Cytogenet 1996 Mar;87(1):4-6 |
PMID 8646739 |
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Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders |
Baxter EJ, Kulkarni S, Vizmanos JL, Jaju R, Martinelli G, Testoni N, Hughes G, Salamanchuk Z, Calasanz MJ, Lahortiga I, Pocock CF, Dang R, Fidler C, Wainscoat JS, Boultwood J, Cross NC |
Br J Haematol 2003 Jan;120(2):251-6 |
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Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study |
Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, Broccardo C |
Blood 2010 Apr 15;115(15):3089-97 |
PMID 20160164 |
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A myeloproliferative disease in two infants associated with eosinophilia and chromosome t(1;5) translocation |
Darbyshire PJ, Shortland D, Swansbury GJ, Sadler J, Lawler SD, Chessells JM |
Br J Haematol 1987 Aug;66(4):483-6 |
PMID 3663504 |
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Cultured autografting for juvenile myelomonocytic leukaemia |
Grainger JD, Will AM, Stevens RF |
Br J Haematol 2002 May;117(2):477-9 |
PMID 11972535 |
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Cytogenetic peculiarities in chronic myelogenous leukemia |
Hild F, Fonatsch C |
Cancer Genet Cytogenet 1990 Jul 15;47(2):197-217 |
PMID 2357695 |
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Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy |
Kern W, Haferlach T, Schnittger S, Ludwig WD, Hiddemann W, Schoch C |
Leukemia 2002 Oct;16(10):2084-91 |
PMID 12357361 |
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Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B-cell lymphoma and multiple myeloma |
Le Baccon P, Leroux D, Dascalescu C, Duley S, Marais D, Esmenjaud E, Sotto JJ, Callanan M |
Genes Chromosomes Cancer 2001 Nov;32(3):250-64 |
PMID 11579465 |
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Molecular diagnosis and targeted therapy of a pediatric chronic eosinophilic leukemia patient carrying TPM3-PDGFRB fusion |
Li Z, Yang R, Zhao J, Yuan R, Lu Q, Li Q, Tse W |
Pediatr Blood Cancer 2011 Mar;56(3):463-6 |
PMID 21072821 |
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AlphaIFN-induced hematologic and cytogenetic remission in chronic eosinophilic leukemia with t(1;5) |
Luciano L, Catalano L, Sarrantonio C, Guerriero A, Califano C, Rotoli B |
Haematologica 1999 Jul;84(7):651-3 |
PMID 10406909 |
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TPM3/PDGFRB fusion transcript and its reciprocal in chronic eosinophilic leukemia |
Rosati R, La Starza R, Luciano L, Gorello P, Matteucci C, Pierini V, Romoli S, Crescenzi B, Rotoli B, Martelli MF, Pane F, Mecucci C |
Leukemia 2006 Sep;20(9):1623-4 |
PMID 16838028 |
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Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia |
Safavi S, Hansson M, Karlsson K, Biloglav A, Johansson B, Paulsson K |
Haematologica 2015 Jan;100(1):55-61 |
PMID 25261097 |
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Development of a dual-color, double fusion FISH assay to detect RPN1/EVI1 gene fusion associated with inv(3), t(3;3), and ins(3;3) in patients with myelodysplasia and acute myeloid leukemia |
Shearer BM, Sukov WR, Flynn HC, Knudson RA, Ketterling RP |
Am J Hematol 2010 Aug;85(8):569-74 |
PMID 20556821 |
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Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase |
Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M |
J Biol Chem 2001 Apr 6;276(14):11189-98 |
PMID 11134006 |
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Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib |
Wilkinson K, Velloso ER, Lopes LF, Lee C, Aster JC, Shipp MA, Aguiar RC |
Blood 2003 Dec 1;102(12):4187-90 |
PMID 12907457 |
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Multiplex fluorescence in situ hybridization in identifying chromosome involvement of complex karyotypes in de novo myelodysplastic syndromes and acute myeloid leukemia |
Xu W, Li JY, Liu Q, Zhu Y, Pan JL, Qiu HR, Xue YQ |
Int J Lab Hematol 2010 Feb;32(1 Pt 1):e86-95 |
PMID 20089000 |
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