Successful treatment of T/myeloid mixed‐phenotype acute leukemia with the translocation (10;11)(p13;q14) <i>PICALM/AF10</i> with 3 + 7 myeloid standard treatment: A case report

Krzisch, Daphné; Zduniak, Alexandra; Veresezan, Elena-Liana; Daliphard, Sylvie; Contentin, Nathalie; Penther, Dominique; Étancelin, Pascaline; Jardin, Fabrice; Camus, Vincent

doi:10.1002/ccr3.3815

Cited by 3 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both in adult patients and children with MPAL, PICALM::MLLT10 is known to be associated with a T/myeloid or B/T subtype (12,13,31,32,34,35). Patient 1 had the T/myeloid phenotype.…”

Section: Discussionmentioning

confidence: 99%

Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL)

PANAGOPOULOS,

ANDERSEN,

JOHANNSDOTTIR

et al. 2023

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of welldefined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients. Patients and Methods: Bone marrow cells were examined using G-banding, array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization. Results: In the first patient, the genetic analyses revealed structural aberrations of chromosomal bands 8p11, 10p11, 11q21, and 17p11, the chimeras MLLT10::PICALM and PICALM::MLLT10, and imbalances (gains/losses) on chromosomes 2, 4, 8, 13, and 21. A submicroscopic deletion in 21q was also found including the RUNX1 locus. In the second patient, there were structural aberrations of chromosome bands 1p32,

show abstract

“…Both in adult patients and children with MPAL, PICALM::MLLT10 is known to be associated with a T/myeloid or B/T subtype (12,13,31,32,34,35). Patient 1 had the T/myeloid phenotype.…”

Section: Discussionmentioning

confidence: 99%

Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL)

PANAGOPOULOS,

ANDERSEN,

JOHANNSDOTTIR

et al. 2023

Cancer Genomics Proteomics

View full text Add to dashboard Cite

show abstract

“…[45] и характеризуется высоким риском рецидива заболевания, в том числе после трансплантации гемопоэтических стволовых клеток [46]. Хотя есть отдельные сообщения об успехе стандартных терапевтических режимов [26], данные более крупных когортных исследований подтверждают неблагоприятное прогностическое значение PICALM::MLLT10 при ОМЛ [47,48]. В соответствии с перечисленными биологическими и клиническими особенностями t(10;11)(p12.31;q14.2) включена в протокол ОМЛ-MRD-2018 в качестве маркера высокого риска.…”

Section: материалы и методыunclassified

Development of Calibration Standards for Minimal Residual Disease Monitoring by Quantitative Reverse Transcription-PCR in AML with t(10;11)(p12.31;q14.2)/ PICALM::MLLT10

Зеркаленкова,

Борковская

2023

Гематология. Трансфузиология. Восточная Европа

View full text Add to dashboard Cite

Хромосомная транслокация t(10;11)(p12.31;q14.2) с образованием химерного гена PICALM::MLLT10 является редкой рекуррентной перестройкой при некоторых типах острых лейкозов, включая острый миелоидный лейкоз (ОМЛ). Она ассоциирована с неблагоприятным прогнозом и в настоящее время включена в риск-стратификацию ОМЛ у детей, получающих терапию по протоколу ОМЛ-MRD-2018, в качестве маркера высокого риска. Экспрессия PICALM::MLLT10 может использоваться в качестве мишени для мониторинга минимальной остаточной болезни (МОБ) методом количественной ПЦР с обратной транскрипцией. Однако в силу редкости и гетерогенности данной перестройки для нее отсутствуют коммерчески доступные калибровочные стандарты. Целью данной работы явилось создание калибровочных стандартов для оценки экспрессии химерного гена PICALM::MLLT10 методом клонирования в плазмидный вектор. Были заклонированы 4 фрагмента PICALM::MLLT10 с различными локализациями точек разрыва в гене MLLT10 (интроны 4, 6, 9 и 10) и локализацией точки разрыва в гене PICALM в интроне 19. Для каждого калибровочного стандарта было показано наличие корректной вставки методом секвенирования по Сэнгеру и отсутствие мутаций в сайтах посадки праймеров и проб для количественной ПЦР. Чувствительность примененных в настоящей работе систем детекции составила 10 копий в реакции в ПЦР с плазмидными стандартами и 1/10 000 в 10-кратных лимитирующих разведениях. Значение углового коэффициента для калибровочных стандартов составило 3,4±0,05, свободного коэффициента – 34,7±1,24, значение R2 превышало 0,95 во всех случаях, коэффициент вариации для образцов с минимальным содержанием молекул-мишеней составил 1,12±0,43%, что соответствует международным рекомендациям для систем детекции и количественных стандартов, применяемых в мониторинге МОБ методом ОТ-ПЦР в режиме реального времени. The chromosomal translocation t(10;11)(p12.31;q14.2) leading to PICALM::MLLT10 fusion gene formation is a rare recurrent rearrangement in some types of acute leukemia, including acute myeloid leukemia (AML). It is associated with a poor prognosis and is currently included in the risk stratification of AML in children receiving therapy according to the AML-MRD-2018 protocol as a high-risk marker. PICALM::MLLT10 expression can be used as a target for minimal residual disease (MRD) monitoring by quantitative reverse transcription-PCR. However, due to the rarity and heterogeneity of this rearrangement, there are no commercially available calibration standards for it. The goal of this work was to create calibration standards for assessing the expression of the chimeric gene PICALM::MLLT10 by cloning into a plasmid vector. Four fragments of PICALM::MLLT10 were cloned with different localizations of breakpoints in the MLLT10 gene (introns 4, 6, 9 and 10) and localization of the breakpoint in the PICALM gene in intron 19. For each calibration standard, the presence of a correct insert was demonstrated by Sanger sequencing and the absence of mutations in the primer binding sites and probes for quantitative PCR. The sensitivity of the detection systems used in this work was 10 copies in a PCR reaction with plasmid standards and 1/10000 in 10-fold limiting dilutions. The slope coefficient for calibration standards was 3.4±0.05, y-intercept was 34.7±1.24, the R2 value exceeded 0.95 in all cases, the coefficient of variation for samples with a minimum content of target molecules was 1.12±0.43%, which corresponds to international recommendations for systems detection and quantitative standards used in real-time RT-PCR monitoring of MRD.

show abstract

“…

…”

mentioning

confidence: 99%

The First Case of Acute Myeloid Leukemia With t(10;11)(p13;q21);PICALM-MLLT10 Rearrangement Presenting With Extensive Skin Involvement

et al. 2022

View full text Add to dashboard Cite

Dear Editor, The PICALM-MLLT10 rearrangement (PICALM-MLLT10r) resulting from t(10;11)(p13;q21) can activate the HOXA gene cluster [1,2], which is considered to be the dominant mechanism underlying leukemic transformation [3,4]. PICALM-MLLT10r occurs in ~10% of T-cell lymphoblastic leukemia/lymphoma cases and is rarely reported in B-cell lymphoblastic leukemia/ lymphoma, mixed-phenotype acute leukemia, lymphoma, and AML [5][6][7]. We report a case of AML with PICALM-MLLT10r presenting with extensive skin lesions. The Institutional Review Board of Samsung Medical Center, Seoul, Korea approved this report and waived the need for informed consent (2022-06-093).A 39-year-old man was admitted to our hospital on February 2022 with erythematous patches on his face and trunk. The lesion had appeared on his face three months before, spread to the trunk and upper extremities, and was suspected to have lymphomatous involvement. Positron emission tomography/computed tomography revealed hypermetabolic lesions in the pancreas, anterior mediastinum, and multiple lymph nodes, including the bilateral neck, supraclavicular, axillary, and mediastinal lymph nodes. Initial complete blood count (CBC) was as follows: white blood cells, 16.69 × 10 9 /L with 75% blasts; Hb, 173 g/L; and platelets, 203 × 10 9 /L. A bone marrow smear showed 83% blasts with hypercellularity (Fig. 1A-F). Flow cytometry analysis revealed that blasts were positive for CD34, cytoplasmic MPO, CD117, CD33, and HLA-DR; weakly positive for CD7, CD64, and CD123; and negative for cytoplasmic and surface CD3, CD19, CD10, cytoplasmic CD22 and CD79a, CD4, and CD56, which was compatible with AML. Leukemic involvement of the skin lesions on the abdomen, back, and flanks in our patient was confirmed via punch biopsy (Fig. 1G-J).Cytogenetic analysis revealed a complex karyotype: 46,XY,t (10;11)(p13;q21),del(17)(p12)[16]/45,idem,der(12)t(12;17) (p12;q21),-del(17)[4] (Fig. 2A). FISH using the Vysis LSI TP53/ CEP17 dual-color probe (Abbott Laboratories, Abbott Park, IL, USA) showed 86.5% of cells with a TP53 deletion. Reverse transcription-PCR for PICALM-MLLT10r was performed using previously reported primers [8]; direct sequencing confirmed the fusion of PICALM exon 19 and MLLT10 exon 3 (Fig. 2B). Targeted next-generation sequencing (NGS) of 46 AML-related genes on NextSeq 550Dx (Illumina,

show abstract

Successful treatment of T/myeloid mixed‐phenotype acute leukemia with the translocation (10;11)(p13;q14) PICALM/AF10 with 3 + 7 myeloid standard treatment: A case report

Cited by 3 publications

References 28 publications

Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL)

Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL)

Development of Calibration Standards for Minimal Residual Disease Monitoring by Quantitative Reverse Transcription-PCR in AML with t(10;11)(p12.31;q14.2)/ PICALM::MLLT10

The First Case of Acute Myeloid Leukemia With t(10;11)(p13;q21);PICALM-MLLT10 Rearrangement Presenting With Extensive Skin Involvement

Contact Info

Product

Resources

About