Molecular and cytogenetic characterization of a new case of t(5;17)(q35;q21) variant acute promyelocytic leukemia

Nicci, Chiara; Ottaviani, Emanuela; Luatti, Simona; Grafone, Tiziana; Tonelli, M; Motta, Maria Rosa; Malagola, Michele; Marzocchi, Giulia; Martinelli, Giovanni; Baccarani, Michele; Testoni, Nicoletta

doi:10.1038/sj.leu.2403645

Cited by 17 publications

(6 citation statements)

References 6 publications

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“…Among the dozen patients with NPM1-RARA, many are pediatric cases [73,[122][123][124][125]. While they received induction with an ATRA-chemotherapy combination, most of them relapsed.…”

Section: Npm-rara T(5;17)(q35;q21)mentioning

confidence: 99%

Classic and Variants APLs, as Viewed from a Therapy Response

Geoffroy

2020

Cancers

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Most acute promyelocytic leukemia (APL) are caused by PML-RARA, a translocation-driven fusion oncoprotein discovered three decades ago. Over the years, several other types of rare X-RARA fusions have been described, while recently, oncogenic fusion proteins involving other retinoic acid receptors (RARB or RARG) have been associated to very rare cases of acute promyelocytic leukemia. PML-RARA driven pathogenesis and the molecular basis for therapy response have been the focus of many studies, which have now converged into an integrated physio-pathological model. The latter is well supported by clinical and molecular studies on patients, making APL one of the rare hematological disorder cured by targeted therapies. Here we review recent data on APL-like diseases not driven by the PML-RARA fusion and discuss these in view of current understanding of “classic” APL pathogenesis and therapy response.

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“…Among the dozen patients with NPM1-RARA, many are pediatric cases [73,[122][123][124][125]. While they received induction with an ATRA-chemotherapy combination, most of them relapsed.…”

Section: Npm-rara T(5;17)(q35;q21)mentioning

confidence: 99%

Classic and Variants APLs, as Viewed from a Therapy Response

Geoffroy

2020

Cancers

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“…[1][2][3][23][24][25][26][27][28] No concrete attempts have so far been made to determine the prevalence of conventional and more recent markers on large series of cases, 1,3,26,27 as well as to draw clear-cut criteria for the differentiation of MS from the plasmacytoid dendritic cell precursor tumor (PMPT) 29,30 (also termed 'natural killer blastic lymphoma'). 1 MS has been described in association with a variety of chromosomal abnormalities 18,[31][32][33][34][35][36][37] as well as with mixed lineage leukemia (MLL) rearrangements. 38,39 In particular, t(8;21)(q22;q22) is regarded as a recurrent aberration in MS. 1 However, review of the literature highlights that such translocation has been detected in tumors more often occurring in childhood and/or at the orbital level.…”

Section: Introductionmentioning

confidence: 99%

Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients

et al. 2006

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Myeloid sarcoma (MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%), CD34 (43.4%), terminal-deoxy-nucleotidyl-transferase (31.5%), CD56 (13%), CD61/linker for activation of T cells (2.2%), CD30 (2.2%) and CD4 (1.1%). Foci of plasmacytoid monocyte differentiation were observed in intestinal cases carrying inv16. Chromosomal aberrations were detected in about 54% of cases: monosomy 7(10.8%), trisomy 8(10.4%) and mixed lineage leukemia-splitting (8.5%) were the commonest abnormalities, whereas t(8;21) was rare (2.2%). The behavior was dramatic irrespective of presentation, age, sex, phenotype and cytogenetics. Most if not all, long survivors received bonemarrow transplantation. The present report expands the spectrum of our knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.

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“…Overall, 4 out of 7 patients (57%) relapsed after first CR (no CNS relapse reported). One patient received an alloHSCT in second CR [3,6,[35][36][37][38][39][40][41].…”

Section: Npm1-rar α Aplmentioning

confidence: 99%

PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Sobas

Talarn-Forcadell

Martínez‐Cuadrón

et al. 2020

Cancers

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It has been suggested that 1–2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

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Molecular and cytogenetic characterization of a new case of t(5;17)(q35;q21) variant acute promyelocytic leukemia

Cited by 17 publications

References 6 publications

Classic and Variants APLs, as Viewed from a Therapy Response

Classic and Variants APLs, as Viewed from a Therapy Response

Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients

PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

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