scholarly journals Acute Myeloid Leukemia Mimicking as Acute Megakaryoblastic Leukemia

2016 ◽  
Vol 2 (2) ◽  
Author(s):  
Dongre T ◽  
Taori H
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Megakaryoblastic Leukemia ◽  
Megakaryoblastic Leukemia ◽  
Acute Myeloid

scholarly journals ACUTE MEGAKARYOBLASTIC LEUKEMIA

2019 ◽  
Vol 25 (3) ◽  
pp. 364
Author(s):  
Yulia Nadar Indrasari ◽  
Ana Murtasyidah
Keyword(s):  
Acute Myeloid Leukemia ◽  
Down Syndrome ◽  
Myeloid Leukemia ◽  
Acute Megakaryoblastic Leukemia ◽  
Megakaryoblastic Leukemia ◽  
Von Willebrand ◽  
Acute Myeloid

Leukemia megakarioblastik akut (AMegL) dibagi dalam tiga kelompok berdasarkan patofiosiolgi, usia, respon terhadap terapi  dan prognosis. Kelompok tersebut adalah AMegL yang terjadi pada anak-anak dengan sindrom Down (DS-AMegL), AMegL yang terjadi pada anak-anak yang tidak memiliki sindrom Down (non-DS-AMegL) dan AMegL pada orang dewasa non-DS (AMegL dewasa). AMegL pada anak tanpa sindrom Down juga disebut leukemia megakarioblastik pediatrik akut atau AMegL anak.1Dasar diagnosis AMegL atau AML M7 menurut FAB adalah adanya sel lini megakariosit 30% atau lebih dari seluruh sel.2 Sedangkan diagnosis AMegL menurut panduan WHO 2016 adalah leukemia akut dengan > 20% blast dimana > 50% adalah lini megakariosit. Sel megakariosit lebih jelas terlihat pada mikroskop elektron yang bereaksi positif terhadap platelet peroksidase2 atau menggunakan antibodi marker terhadap CD41/gpIIb, CD42b/gpIb, CD61/gpIIIa, faktor Von Willebrand dan pengecatan LAT.3 Temuan sitogenetika berbeda antara ketiga jenis AMegL sesuai dengan perbedaan patofisiologinya. WHO (2016) menyebutkan  leukemia megakarioblastik akut ke dalam kriteria AML not otherwise specific (NOS). AmegL adalah leukemia akut dengan > 20% blast dimana > 50% adalah lini megakariosit. Kriteria ini mengeksklusi AML dengan mielodisplasia (acute myeloid leukemia with myelodysplasia related change; AMLMRC), AML yang berhubungan dengan terapi, dan AML dengan kelainan genetik rekuren, seperti AML dengan t(1;22)(p13.3;q13.1), inv(3)(q21.3q26.2), atau t(3;3)(q21.3;q26.2). DS-AMegL juga diklasifikasikan sendiri ke dalam Myeloid Leukemia associated Down Syndrome.3Prognosis AMegL pada pasien dewasa yang diobati jauh di bawah bentuk AMegL lainnya. Waktu kelangsungan hidup rata-rata hanya 18 hingga 41 minggu dengan tingkat kelangsungan hidup 5 tahun hanya 10-11 persen. Perbaikan besar dalam statistik ini kemungkinan akan membutuhkan pendekatan pengobatan baru yang diarahkan pada mekanisme yang mendasari penyakit ini.1

scholarly journals Infant Acute Myeloid Leukemia: A Unique Clinical and Biological Entity

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 777
Author(s):  
Charlotte Calvo ◽  
Odile Fenneteau ◽  
Guy Leverger ◽  
Arnaud Petit ◽  
André Baruchel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Study Groups ◽  
Biological Entity ◽  
Age Group ◽  
Older Children ◽  
Megakaryoblastic Leukemia ◽  
Acute Myeloid

Infant acute myeloid leukemia (AML) is a rare subgroup of AML of children <2 years of age. It is as frequent as infant acute lymphoblastic leukemia (ALL) but not clearly distinguished by study groups. However, infant AML demonstrates peculiar clinical and biological characteristics, and its prognosis differs from AML in older children. Acute megakaryoblastic leukemia (AMKL) is very frequent in this age group and has raised growing interest. Thus, AMKL is a dominant topic in this review. Recent genomic sequencing has contributed to our understanding of infant AML. These data demonstrated striking features of infant AML: fusion genes are able to induce AML transformation without additional cooperation, and unlike AML in older age groups there is a paucity of associated mutations. Mice modeling of these fusions showed the essential role of ontogeny in the infant leukemia phenotype compared to older children and adults. Understanding leukemogenesis may help in developing new targeted treatments to improve outcomes that are often very poor in this age group. A specific diagnostic and therapeutic approach for this age group should be investigated.

Pediatric Acute Myeloid Leukemia with Nucleophosmin Mutations Is Characterized by a Gene Expression Signature with Dysregulated HOX Gene Expression Distinct from MLL-Rearranged Leukemias.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2993-2993
Author(s):  
Charles G. Mullighan ◽  
Alyssa L. Kennedy ◽  
Xiaodong Zhou ◽  
Sheila A. Shurtleff ◽  
James R. Downing
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Expression Signature ◽  
Fusion Partner ◽  
Mutation Status ◽  
Cytogenetic Abnormalities ◽  
Megakaryoblastic Leukemia ◽  
Normal Cytogenetics ◽  
Acute Myeloid

Abstract Recent studies have identified mutations in the nucleophosmin (NPM) gene in up to one-third of cases of acute myeloid leukemia (AML) lacking a recurring cytogenetic abnormality. NPM mutations (NPMm+) result in aberrant cytoplasmic localization of nucleophosmin, which may potentially perturb multiple cellular pathways including cell cycle regulation. However the exact mechanisms by which mutant NPM contributes to leukemogenesis are unclear. Gene expression analysis may identify mediators or pathways in NPMm+ AML that are important in the development of leukemia. We have examined NPM mutation status in a 93 cases of pediatric AML and correlated mutation status with gene expression profile. All major AML subgroups were studied including AML-ETO (n=18), MLL rearranged (n=14) CBFB-MYH11 (n=13), PML-RARA and variants (n=4), acute megakaryoblastic leukemia (n=4), and AML with normal cytogenetics (n=20), or non-recurring cytogenetic abnormalities (n=20). Exon 12 of NPM was PCR amplified, sequenced, and abnormal cases verified by cloning and sequencing. Gene expression profiling was performed using Affymetrix U133A arrays. Six cases with tetranucleotide insertion mutations in NPM exon 12 were identified. Four had normal cytogenetics, and two non-recurring cytogenetic abnormalities. Differential gene expression between NPMm+ and NPMm- AML (either all NPMm- cases, or only those NPMm- cases lacking recurring cytogenetic abnormalities) was assessed by t-test. NPMm+ AML was characterized by upregulation of multiple homeobox genes (e.g. HOXA9, A10, B2, B6) as well as multiple genes with known or potential roles in tumorigenesis, such as MEIS1 and the NPM fusion partner ALK. This pattern of disordered HOX expression is similar to that of MLL-rearranged leukemia; however comparison of the signatures of NPMm+ and MLL-rearranged leukemia identified important differences, such as upregulation of HOXB2, B3, B6 and D4 in NPMm+ AML but not MLL-leukemia. These results confirm a recently published report describing perturbed HOX expression in NPMm+ AML (Alcalay et al. Blood2005;106:899), and provide the first evidence that the NPMm+ signature is similar to but distinct from MLL-rearranged AML. These findings provide important insights into the pathogenesis of NPMm+ leukemia, and support the hypothesis that mutated NPM dysregulates HOX expression via a different mechanism than MLL rearrangement.

Leukemia-Initiating Cells in Acute Megakaryoblastic Leukemia and Transient Leukemia of Down Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3377-3377
Author(s):  
Jian Chen ◽  
Yue Li ◽  
Monica Doedens ◽  
John E. Dick ◽  
Alvin Zipursky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Human Cells ◽  
Acute Megakaryoblastic Leukemia ◽  
Cell Injection ◽  
Megakaryoblastic Leukemia ◽  
Transient Leukemia ◽  
Human Acute Myeloid Leukemia ◽  
The Right ◽  
Acute Myeloid

Abstract Background. Children with Down syndrome (DS) have a 500-fold greater risk of developing Acute Megakaryoblastic Leukemia (AMKL) than the general population. In addition, approximately one out of ten newborns with DS has circulating blasts in the blood, a condition termed Transient Leukemia (TL). Unlike AMKL, TL resolves spontaneously within three months but in about 20% of cases is followed by AMKL later in life. Both the blasts of TL and AMKL of DS (DS-AMKL) show megakaryocytic differentiation and both harbor somatic mutations of GATA1, resulting in the expression of the N-terminally truncated mutant protein GATA1s. We hypothesize that the difference between the reversible and irreversible phenotype of TL and AMKL in DS, respectively, is due to a functional difference of the leukemia-initiating cells in both conditions. Methods. To characterize the leukemia-initiating cells we established experimental models of AMKL and TL of DS by transplanting cryopreserved primary human cells into NOD/SCID mice. Cell doses ranging from 0.5 to 20x106 were injected intrafemorally into 8-week-old irradiated recipients, which had also been treated with anti-NK cell antibody (anti-CD122). Human hematopoietic growth factors (stem cell factor, interleukin-3 and thrombopoietin) were administered intraperitoneally during the first two weeks following transplantation. Phenotypic analysis using standard cytological, histological and flowcytometric methods was carried out approximately 8 weeks after transplantation. Results. Recipients transplanted with 2 (of a total of 7) AMKL samples showed engraftment with 32% (range 26–44%; n=3) and 73% (range 16–95%; n=8) human cells at the site of the original cell injection (right femur) and 15% (n=3) and 38% (n=8) at distant medullary sites. The engrafted human cells were trisomic for human chromosome 21, expressed the megakaryocytic marker CD61 and, compared with the transplanted primary AMKL cell population, harbored the concordant GATA1 mutation. Bone marrow biopsy revealed increased reticulin fibres 8 weeks after transplantation of AMKL cells. In our experiments, DS-AMKL-initiating cells were found to occur within a broad range of frequency (18x10−4 to 20x10−6) but were not defined by their expression of CD34 and/or CD38. In keeping with the self-renewal capacity of leukemia-initiating cells in human acute myeloid leukemia, DS-AMKL cells collected from the right femur (site of initial cell injection) and from distant bone marrow sites of primary recipients were able to engraft secondary recipients. In contrast, only one of five primary TL cell samples showed engraftment within the right femur (21%, range 3–81%; n=5), the site at which TL cells had been injected 8 weeks earlier. No TL cells or engrafted human cells were detected in any distal bone marrow site or extramedullary compartment such as the spleen. Conclusion. Our results indicate that the function of leukemia-initiating cells in DS-AMKL but not TL parallels those of non-DS human acute myeloid leukemia. Our model provides an experimental approach to distinguish the role of the cellular target vs. mutations cooperating with GATA1 mutations in the development of AMKL and TL in DS.

scholarly journals First reported case of acute megakaryoblastic leukemia successfully treated with decitabine and venetoclax combined with imatinib

2021 ◽  
Author(s):  
Wanzhuo Xie
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Targeted Drugs ◽  
Acute Megakaryoblastic Leukemia ◽  
Rare Type ◽  
Megakaryoblastic Leukemia ◽  
First Case ◽  
Acute Megakaryocytic Leukemia ◽  
Acute Myeloid

Abstract Acute megakaryocytic leukemia (AMKL) is a rare type of acute myeloid leukemia (AML), which is characterized by its effect on megakaryocytes in bone marrow. Despite standard doses of anthracycline plus cytarabine based regimen, AMKL is notorious for its poor prognosis. With the continuous development of targeted drugs, the choice of chemotherapy regimens for AML patients has been gradually enriched. However, as far as we known, there is little data with this regimen in AMKL with decitabine and Bcl-2 inhibitor combined with imatinib. Herein, we reported the first case of adult AMKL with BCR-ABL positive successfully treated with decitabine and venetoclax combined with imatinib.

scholarly journals New treatment regimen for acute megakaryoblastic leukemia with BCR-ABL positive: case report and literature review

2021 ◽  
Author(s):  
Huafei Shen ◽  
Yuanfei Shi ◽  
Xiaolong Zheng ◽  
Jie Jin ◽  
Wanzhuo Xie
Keyword(s):  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Targeted Drugs ◽  
Acute Megakaryoblastic Leukemia ◽  
Rare Type ◽  
Megakaryoblastic Leukemia ◽  
First Case ◽  
New Treatment ◽  
Acute Megakaryocytic Leukemia ◽  
Acute Myeloid

Abstract Acute megakaryocytic leukemia (AMKL) is a rare type of acute myeloid leukemia (AML), which is characterized by its effect on megakaryocytes in bone marrow. Despite standard doses of anthracycline plus cytarabine based regimen, AMKL is notorious for its poor prognosis. With the continuous development of targeted drugs, the choice of chemotherapy regimens for AML patients has been gradually enriched. However, as far as we known, there is little data with this regimen in AMKL with decitabine and Bcl-2 inhibitor combined with imatinib. Herein, we reported the first case of adult AMKL with BCR-ABL positive successfully treated with decitabine and venetoclax combined with imatinib.

scholarly journals Immunophenotypic characterization of acute megakaryoblastic leukaemia in children

2019 ◽  
Vol 18 (3) ◽  
pp. 35-40
Author(s):  
M. Yu. Alexenko ◽  
O. I. Illarionova ◽  
N/ Yu. Verzhbitskaya ◽  
E. A. Zerkalenkova ◽  
I. A. Novikova ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Trisomy 21 ◽  
Myeloid Leukemia ◽  
Antigen Expression ◽  
Megakaryoblastic Leukemia ◽  
Pediatric Hematology ◽  
National Medical ◽  
High Level ◽  
Acute Myeloid

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia, in which the bone marrow produce increased numbers of immature abnormal megakaryoblasts. AMKL is rare both in children and adults, but is the most frequent subtype of acute myeloid leukemia (AML) in children with Down syndrome. Morphological diagnosis of this disease could be complicated, thus flow cytometry plays a crucial role in the diagnostics of AMKL. The aim of the present study was to investigate the immunophenotypic characteristics of AMKL in children. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The study group included 103 patients with AMKL. Antigen expression profile was assessed by multicolor flow cytometry. We identified three groups of patients according to different levels of CD45 expression, and in majority of patients (74%) high level of CD45 expression was detected. Significant immunophenotypic differences between these groups were found. In 56% of patients trisomy of 21 chromosome was detected. Among these patients, 86% belonged to group of high CD45 expression. Moreover, children with trisomy 21 represented the majority in the group with high level of CD45 expression (64%). Also, there were found several significant differences between patients with and without trisomy 21 within the group of high CD45 expression. This study demonstrated the wide immunophenotypic heterogeneity of AMKL. In general, the revealed diversity obviously reflects the biological heterogeneity of this AML subtype. 

scholarly journals Acute Megakaryoblastic Leukemia with Trisomy 21 and Tetrasomy 21 Clones in a Phenotypically Normal Child with Mosaic Trisomy 21

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Eric Won ◽  
Tanja A. Gruber ◽  
Suzanne Tucker ◽  
Deborah E. Schiff
Keyword(s):  
Normal Child ◽  
Trisomy 21 ◽  
Myeloid Leukemia ◽  
Pediatric Patients ◽  
Acute Megakaryoblastic Leukemia ◽  
Megakaryoblastic Leukemia ◽  
Favorable Prognosis ◽  
Reduced Intensity ◽  
Acute Myeloid ◽  
Mosaic Trisomy

Pediatric acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) that may be divided into two subgroups: (1) Down syndrome- (DS-) related AMKL which generally has a favorable prognosis and (2) non-DS-related AMKL which generally has a poorer outcome. We report a phenotypically normal child with AMKL with trisomy 21 (T21) and tetrasomy 21 clones. Subsequently, she was diagnosed with mosaic T21. She underwent reduced-intensity therapy with good outcome. We review the literature regarding AMKL-associated cytogenetic abnormalities and AMKL in association with DS. We suggest evaluation for mosaic T21 in phenotypically normal pediatric patients with T21-positive AML.

Sign in / Sign up

Export Citation Format

Share Document