B-cell acute lymphoblastic leukemia as evolution of a 8p11 myeloproliferative syndrome with t(8;22)(p11;q11) and BCR-FGFR1 fusion gene

Baldazzi, Carmen; Iacobucci, Ilaria; Luatti, Simona; Ottaviani, Emanuela; Marzocchi, Giulia; Paolini, Stefania; Stacchini, Monica; Papayannidis, Cristina; Gamberini, Carla; Martinelli, Giovanni; Baccarani, Michele; Testoni, Nicoletta

doi:10.1016/j.leukres.2010.05.009

Cited by 32 publications

(33 citation statements)

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“…The administration of any large-molecule therapeutic, such as a mAb, potentially induces an unwanted immune response through the development of antidrug antibodies (ADAs) [1][2][3]. In clinical studies of eculizumab in patients with PNH, the development of HAHAs was transient and very infrequent with minimal impact on clinical response [4][5][6]. This current laboratory study, M07-003 (registered at http://www.clinical trials.-gov as NCT01412047), addresses a postapproval commitment to the FDA and the European Medicines Agency (EMA) to examine immunogenicity of eculizumab after longterm treatment.…”

Section: Assessment Of Human Antihuman Antibodies To Eculizumab Aftermentioning

confidence: 99%

“…The development of neutralizing and non-neutralizing HAHAs associated with eculizumab use was assessed in patients with PNH who participated in the open-label, long-term study E05-001 [7]. Briefly, the study included 195 patients with PNH who participated in three prospective trials: a phase two pilot study [5]; and two phase three studies [4,6]. The E05-001 study comprised a 104-week treatment period and a 16-week post-treatment follow-up period for patients who terminated treatment early [7].…”

Section: Assessment Of Human Antihuman Antibodies To Eculizumab Aftermentioning

confidence: 99%

“…The case with t(8;22) has been previously reported by our group. She presented with B-cell acute lymphoblastic leukemia (B-ALL) and complex karyotype with abnormalities targeting genes involved in lymphoid development [5]. A diagnosis of chronic myelomonocytic leukemia (CMML) with eosinophilia but without lymph nodes involvement was made in the patient with t(8;9).…”

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FGFR1 and KAT6A rearrangements in patients with hematological malignancies and chromosome 8p11 abnormalities: biological and clinical features

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confirm that mutant PDGFRB is indeed the driver mutation in PDGFRB rearranged myeloid neoplasms, consistent with the robust treatment responses with imatinib, thereby constituting a unique stem cell disorder that should continue to be classified separately. To the Editor: Chromosomal 8p11 abnormalities are rare but recurrent in hematological malignancies and frequently involve the FGFR1 or KAT6A genes. FGFR1 rearrangements are associated with the 8p11 Myeloproliferative Syndrome (EMS), characterized by myeloproliferative neoplasms (MPN) with eosinophilia; lymphadenopathy, usually Tlymphoblastic lymphoma/leukemia (T-LBL); and progression to acute myeloid leukemia (AML) [1]. The 2008 WHO classification of hematopoietic and lymphoid neoplasms classified it as "myeloid and lymphoid neoplasms with FGFR1 abnormalities" in the "myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1" category [2]. However, EMS patients, different from patients with PDGFRA and PDGFRB rearrangements, are not sensitive to imatinib therapy. KAT6A rearrangements are associated with aggressive forms of M4-M5 AML, distinctive bone marrow (BM) morphology (e.g. erythrophagocytosis), extramedullary involvement and disseminated intravascular coagulation [3]. In this study, we report the frequency of FGFR1 and KAT6A involvement in patients with 8p11 abnormalities, and the correlation with clinical features.By cytogenetic analysis, we identified 12 patients (0.3%) with chromosome 8p11 abnormalities over 4207 patients diagnosed with myeloid or lymphoid malignancies. A commercially available FGFR1 dual color breakapart probe (Kreatech Diagnostics, The Netherlands) and a KAT6A dual color breakapart probe, designed from bacterial artificial chromosomes (BACs), were used to investigate FGFR1 and KAT6A genes by fluorescence in situ hybridization (FISH). BACs RP11-231D20 and RP11-108L9, mapping 5 0 and 3 0 of KAT6A according to Ensembl (http://www.ensembl.org/), were supplied marked in Spectrum Green and Spectrum Orange, respectively (BlueFISH, Illumina, US) (Supporting Information, Fig. S1).Patients' clinical and cytogenetic characteristics and FISH results are shown in Table I. KAT6A rearrangement was identified in four cases. Two cases had inv(8)(p11q13), one showed t(8;16)(p11;p13) and one had t(8;20)(p11;q13). FISH analysis revealed KAT6A involvement with classical FISH signal pattern in three cases while one patient showed an atypical signal pattern, indicating a deletion 3 0 of KAT6A ( Supporting Information, Fig. S2A,B). Patients with KAT6A rearrangements showed common features such as young age and AMLs with involvement of monocytic lineage. Furthermore, they were associated with extramedullary localization and exposition to previous chemotherapy. No sign of erythrophagocitosis was observed in our cases despite it has been frequently associated with KAT6A rearrangements [3]. In the patient with t(8;16), BM showed 60% of erythroid and 40% of monocytoid blast cells, therefore a diagnosis of AML-M6 ...

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Section: Assessment Of Human Antihuman Antibodies To Eculizumab Aftermentioning

confidence: 99%

Section: Assessment Of Human Antihuman Antibodies To Eculizumab Aftermentioning

confidence: 99%

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confidence: 99%

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FGFR1 and KAT6A rearrangements in patients with hematological malignancies and chromosome 8p11 abnormalities: biological and clinical features

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“…Recently, certain studies have reported that patients with t(8;22) exhibit similar morphological and clinical features to those observed in CML patients (2)(3)(4). Since the first case reported by Fioretos in 2001 (5), to the best of our knowledge, t(8;22)(p11;q11) has been reported in only 17 cases with hematological malignancies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Of these, 6 cases presented with atypical CML (2-4,6,7), 3 with myeloproliferative neoplasms (5,8,9), 3 with B-cell acute lymphoblastic leukemia (10-12) and 5 with other types of hematological neoplasms (13)(14)(15)(16)(17).…”

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confidence: 82%

“…Of the 15 patients with laboratory data, 13 patients showed an increased WBC count (median, 5.56x10 10 /l; range, 1.84-19.8x10 10 /l), while the remaining 2 displayed a normal and a decreased WBC count of 5.1x10 9 /l (13) and 1.5x10 9 /l (16), respectively. Among the 15 cases, 10 displayed a decreased Hb level (median, 108 g/l; range, 72-131 g/l) (4,5,(9)(10)(11)(13)(14)(15)(16)(17), and the majority of these cases exhibited a marginal decrease in Hb levels. While 2 out of the 15 patients showed increased Plt levels (9,13), decreased levels were observed in 4 cases (11,(14)(15)(16) and the remaining 9 displayed normal levels.…”

Section: Discussionmentioning

confidence: 99%

Chronic myelogenous leukemia-like hematological malignancy with t(8;22) in a 26-year-old pregnant woman: A case report

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Abstract. t(8;22)(p11;q11) is a rare but recurrent genetic alteration in various hematological disorders. Patients with t(8;22)(p11;q11) may be misdiagnosed with chronic myelogenous leukemia (CML), due to the similar clinical features. Thus, the current study presents a patient with t(8;22) (p11;q11) who was previously misdiagnosed with CML in the chronic phase. The current patient was a 26-year-old woman who was 4-weeks pregnant and in whom an increased white blood cell count (4.0x10 10 /l) was found upon physical examination. The patient had no history of hematological disease. Although cytogenetics showed a normal karyotype and no breakpoint cluster region/Abelson murine leukemia viral oncogene homolog 1 (BCR/ABL) fusion gene was detected by reverse transcription-polymerase chain reaction, a diagnosis of chronic myelogenous leukemia (CML) was initially made according to the clinical and morphological features. Another 6 weeks later, t(8;22)(p11;q11) rearrangement was present in 9 out of 10 analyzed metaphases. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction indicated a negative result for the BCR/ABL fusion, but gave a positive result for the BCR-fibroblast growth factor receptor 1 fusion. A hematological diagnosis of atypical CML was again formed. IntroductionChronic myelogenous leukemia (CML) is characterized by the presence of the Philadelphia chromosome, which is generated by the reciprocal translocation, t(9;22) (1). This abnormality is found in >90% of CML cases, in 15-20% of acute lymphoblastic leukemia cases, and a small number of acute myeloid leukemia cases (1). Recently, certain studies have reported that patients with t(8;22) exhibit similar morphological and clinical features to those observed in CML patients (2-4). Since the first case reported by Fioretos in 2001 (5), to the best of our knowledge, t(8;22)(p11;q11) has been reported in only 17 cases with hematological malignancies (2-17). Of these, 6 cases presented with atypical CML (2-4,6,7), 3 with myeloproliferative neoplasms (5,8,9), 3 with B-cell acute lymphoblastic leukemia (10-12) and 5 with other types of hematological neoplasms (13-17). t(8;22) results in an in-frame fusion of FGFR1 on 8p11 and BCR on 22q11, and causes constitutive activation of the tyrosine kinase of the breakpoint cluster region/fibroblast growth factor receptor 1 (BCR/FGFR1) chimera protein, similar to Abelson murine leukemia viral oncogene homolog 1 (ABL) kinase activity in the BCR/ABL chimera (2,18).The present study reports the 18th case of a CML-like hematological tumor bearing t(8;22)(p11;q11) with no other cell lineages involved. Case reportOn February 23, 2013, a 26-year-old woman who was 4-weeks pregnant, with no history of hematological disease, was found to exhibit an increased white blood cell (WBC) count (4.0x10 10 /l; normal range, 0.37-0.92x10 10 /l) upon physical examination. Cytogenetic study on the patient's bone marrow (BM) cells showed a normal female karyotype in all metaphases. Tests for the BCR/ABL fusion ...

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Chronic myeloproliferative neoplasms

Vandenberghe¹,

Michaux²

2015

Cancer Cytogenetics

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B-cell acute lymphoblastic leukemia as evolution of a 8p11 myeloproliferative syndrome with t(8;22)(p11;q11) and BCR-FGFR1 fusion gene

Cited by 32 publications

References 9 publications

FGFR1 and KAT6A rearrangements in patients with hematological malignancies and chromosome 8p11 abnormalities: biological and clinical features

FGFR1 and KAT6A rearrangements in patients with hematological malignancies and chromosome 8p11 abnormalities: biological and clinical features

Chronic myelogenous leukemia-like hematological malignancy with t(8;22) in a 26-year-old pregnant woman: A case report

Chronic myeloproliferative neoplasms

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