ABSTRACT
We report a female newborn with acute myelogenous leukemia (AML) associated with a MYB-GATA1 fusion gene. Morphologic findings of myeloid lineage were obtained using light microscopy. Cytogenetic analysis of peripheral blood showed a complex karyotype: 46,X,-X,add(3)(q21),der(6)add(6)(q21)del(6)(q?), +mar1[5]/46,XX[15]. Targeted RNA sequencing revealed a MYB-GATA1 fusion gene. Reduced-dose AML-type chemotherapy resulted in remission and survival for >3 years without relapse. The present case demonstrated the feasibility of carrying out targeted RNA sequencing for identifying MYB-GATA1 and supports the notion that neonatal AML with MYB-GATA1 with reduced chemotherapy may show better prognosis than other highly toxic therapies.
Subject(s)
Chromosome Aberrations , GATA1 Transcription Factor/genetics , Infant, Newborn, Diseases , Leukemia, Myeloid, Acute , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins c-myb/genetics , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/drug therapy , Infant, Newborn, Diseases/genetics , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/drug therapyABSTRACT
No disponible
Subject(s)
Humans , Female , Infant , Leukemia, Myeloid, Acute/diagnosis , Skin/pathology , Leukemia, Myeloid, Acute/congenitalSubject(s)
Leukemia, Myeloid, Acute/diagnosis , Skin/pathology , Female , Humans , Infant , Leukemia, Myeloid, Acute/congenitalSubject(s)
Histone-Lysine N-Methyltransferase/genetics , Leukemia, Myeloid, Acute/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/administration & dosage , Exanthema/congenital , Exanthema/genetics , Female , Gene Rearrangement/genetics , Humans , Infant, Newborn , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/drug therapy , Mitoxantrone/administration & dosageSubject(s)
Leukemia, Myeloid, Acute/genetics , Neoplasm Regression, Spontaneous , Oncogene Proteins, Fusion/genetics , Skin Neoplasms/genetics , Bone Marrow/pathology , E1A-Associated p300 Protein/genetics , Female , Gene Rearrangement , Histone Acetyltransferases/genetics , Humans , Infant, Newborn , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/pathology , Skin Neoplasms/congenital , Skin Neoplasms/pathologyABSTRACT
We report the first case of a fetus with acute myeloid leukemia, without Down syndrome, diagnosed in utero. A cordocentesis sample prepared to investigate hepatomegaly led to further evaluations revealing acute myeloid leukemia, monocytic type, in the fetus. Cytogenetic analysis showed mixed lineage leukemia duplication, no gene disruption or trisomy. Planned treatment included intrauterine exchange transfusion to extend gestation, low-dose chemotherapy at birth, and full chemotherapy once stable. Before any intervention, the child was delivered emergently for maternal condition and died 2 hours later. Although it is now possible to diagnose hematologic malignancy in a fetus, there is little information to direct management.
Subject(s)
Fetal Diseases/diagnosis , Leukemia, Myeloid, Acute/congenital , Cordocentesis , Female , Humans , Pregnancy , Prenatal DiagnosisABSTRACT
Cytogenetics can inform risk stratification in pediatric acute myeloid leukemia (AML). We describe the first case of a newborn with leukemia cutis found to have AML harboring a cryptic insertional t(8;16)(p11.2;p13.3) with associated KAT6A/CREBBP fusion identified exclusively by fluorescence in situ hybridization (FISH). Expectant management resulted in spontaneous leukemia resolution. The identification of t(8;16)(p11.2;p13.3) may serve as a biomarker for spontaneous remission in congenital AML. FISH for this translocation is warranted in congenital AML with a normal karyotype, and patients with KAT6A/CREBBP fusion should be conservatively managed. While 50% of spontaneously remitting congenital AML with t(8;16)(p11.2;p13.3) may recur, high salvage rates are attained with standard therapy.
Subject(s)
CREB-Binding Protein/genetics , Histone Acetyltransferases/genetics , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/genetics , Neoplasm Regression, Spontaneous/genetics , Translocation, Genetic/genetics , Chromosomes, Human, Pair 8/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Karyotype , Oncogene Proteins, Fusion/geneticsSubject(s)
Leukemia, Myeloid, Acute/pathology , Neoplasm Regression, Spontaneous , Skin Neoplasms/pathology , Female , Histone-Lysine N-Methyltransferase/genetics , Humans , Infant , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Skin Neoplasms/genetics , Translocation, Genetic/geneticsABSTRACT
The treatment of patients with congenital leukemia is difficult and often results in a poor prognosis. We present here the case of a female child with congenital acute myeloid leukemia (AML) with t(8 ; 16) (p11 ; p13) who received chemotherapy and survived for more than 10 years without relapse. A novel MOZ-CBP chimera was found in her diagnostic sample. Although adult AML patients with MOZ-CBP have mainly been reported as having therapy-related AML and showed poor prognoses, the present case supports the idea that AML with MOZ-CBP in the pediatric population might show better prognoses.
Subject(s)
Leukemia, Myeloid, Acute/congenital , Oncogene Proteins, Fusion/genetics , Chromosomes, Human, Pair 16 , Chromosomes, Human, Pair 8 , Female , Gene Rearrangement , Humans , Infant, Newborn , Leukemia, Myeloid, Acute/genetics , RNA, Neoplasm/analysis , Sequence Analysis, RNA , SurvivorsABSTRACT
The multidisciplinary management of a male neonate presenting with congenital acute myelogenous leukemia of monoblastic phenotype is reported using conventional chemotherapy, high dose conditioning, and matched unrelated donor stem cell transplantation. These therapies were combined to add a graft versus leukemia effect to the treatment. Although chimerism studies showed a decrease of donor white blood cells, T-cells remained stable of allogeneic origin. We hypothesize that a continuous graft versus leukemia effect results in minimal residual disease negativity for now more than 18 months since stem cell transplantation.
Subject(s)
Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/therapy , Stem Cell Transplantation , Graft vs Leukemia Effect , Humans , Infant, Newborn , Leukemia, Myeloid, Acute/pathology , Male , Patient Care TeamABSTRACT
We presents an infant with several indurated plaques and nodules scattered on her body. She was brought to the hospital because of fever, runny nose and cough from one month ago. During the examination and investigation the plaques and nodules grabbed the attention of the clinicians and the skin biopsy and other lab works revealed the diagnosis of congenital leukemia.
Subject(s)
Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/diagnosis , Pneumonia/diagnosis , Diagnosis, Differential , Female , Humans , InfantABSTRACT
Acute myeloid leukemia (AML) with t(8;16)(p11;p13) is known to have very poor prognosis in adults. In contrast, the prognosis is not clear in pediatric patients and chemotherapy is generally started immediately in cases of congenital leukemia because of its association with hyperleukocytosis and poor prognosis. This study reports a case of congenital AML where chemotherapy was discontinued after detection of a MOZ-CBP fusion, which remains in remission without additional treatment. This article stresses the importance of examination for the presence of the MOZ-CBP fusion at diagnosis to inform treatment decisions in congenital AML.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 8/genetics , Genetic Testing/statistics & numerical data , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/genetics , Oncogene Proteins, Fusion/genetics , Translocation, Genetic/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Leukemia, Myeloid, Acute/drug therapy , Prognosis , RNA, Messenger/genetics , Remission Induction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a subtype of acute myeloid leukemia, affecting mainly the elderly. It is thought to be derived from plasmacytoid dendritic cell precursors, which frequently present as cutaneous lesions. We have made a detailed analysis of an infant with BPDCN, who manifested with hemophagocytic lymphohistiocytosis. The peripheral blood leukocytes revealed the t(2;17;8)(p23;q23;p23) translocation and a CLTC-ALK fusion gene, which have never been reported in BPDCN or in any myeloid malignancies thus far. Neonatal blood spots on the patient's Guthrie card were analyzed for the presence of the CLTC-ALK fusion gene, identifying the in utero origin of the leukemic cell. Although the leukemic cells were positive for CD4, CD56, CD123, and CD303, indicating a plasmacytoid dendritic cell phenotype, detailed analysis of the lineage distribution of CLTC-ALK revealed that part of monocytes, neutrophils, and T cells possessed the fusion gene and were involved in the leukemic clone. These results indicated that leukemic cells with CLTC-ALK originated in a multipotent hematopoietic progenitor in utero. This is the first report of the CLTC-ALK fusion gene being associated with a myeloid malignancy, which may give us an important clue to the origin of this rare neoplasm.
Subject(s)
Dendritic Cells/pathology , Leukemia, Myeloid, Acute/genetics , Oncogene Proteins, Fusion/genetics , Chromosomes, Human, Pair 2/genetics , Female , Gene Fusion , Humans , Infant , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/pathologyABSTRACT
Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. Although most cases are accompanied by MLL rearrangements and harbor very few somatic mutations, less is known about the genetics of the cases without MLL translocations. We performed the largest exome-sequencing study to date on matched non-cancer DNA from pairs of mothers and IL patients to characterize congenital variation that may contribute to early leukemogenesis. Using the COSMIC database to define acute leukemia-associated candidate genes, we find a significant enrichment of rare, potentially functional congenital variation in IL patients compared with randomly selected genes within the same patients and unaffected pediatric controls. IL acute myeloid leukemia (AML) patients had more overall variation than IL acute lymphocytic leukemia (ALL) patients, but less of that variation was inherited from mothers. Of our candidate genes, we found that MLL3 was a compound heterozygote in every infant who developed AML and 50% of infants who developed ALL. These data suggest a model by which known genetic mechanisms for leukemogenesis could be disrupted without an abundance of somatic mutation or chromosomal rearrangements. This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins.
Subject(s)
Biomarkers, Tumor/genetics , Gene Rearrangement , Leukemia, Myeloid, Acute/genetics , Mutation/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Polymorphism, Single Nucleotide/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adult , Case-Control Studies , Child , Female , Histone-Lysine N-Methyltransferase , Humans , Infant , Leukemia, Myeloid, Acute/congenital , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/congenital , Prognosis , Survival Rate , Young AdultSubject(s)
Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 1 , Leukemia, Myeloid, Acute/congenital , Leukemia, Myeloid, Acute/genetics , Translocation, Genetic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fatal Outcome , Female , Humans , Infant, Newborn , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapyABSTRACT
Congenital leukaemia (CL) is a rare malignancy that accounts for < 1% of cases of childhood leukaemias. Leukaemia cutis (LC) refers to cutaneous infiltration with leukaemic cells, and is seen in 30-50% of CL cases. It may precede, follow or occur simultaneously with leukaemia. If left untreated, the prognosis is usually poor, but early diagnosis and treatment may result in a favourable prognosis. We report a case of congenital leukaemia cutis with a progressive, violaceous papulonodular eruption (a 'blueberry muffin' rash), which had been noted at birth, as a presenting sign of acute myeloid leukaemia (AML), which on investigation was classified as AML, FAB M2 type with a t(8; 21)(p11;q22) chromosomal defect. The patient had a favourable response to AML chemotherapy.
Subject(s)
Leukemia, Myeloid, Acute/congenital , Skin Neoplasms/congenital , Female , Humans , Infant, Newborn , Leukemia, Myeloid, Acute/pathology , Skin Neoplasms/pathologySubject(s)
Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 21/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Mutation/genetics , Translocation, Genetic , Female , Genetic Predisposition to Disease , Genome, Human , High-Throughput Nucleotide Sequencing , Humans , Leukemia, Myeloid, Acute/congenital , Male , PedigreeABSTRACT
Congenital leukemia is infrequent, occurring in <1% of pediatric leukemia patients, and mainly of myeloid lineage. Twenty-five to 30% of congenital leukemia cases present with cutaneous leukemic infiltrates. Rarely, infants will have aleukemic leukemia cutis, presenting with leukemic skin lesions but without systemic symptoms or bone marrow involvement. Few cases of congenital aleukemic leukemia cutis have been reported in the literature. The course of disease is variable as cases of spontaneous resolution have been described. Here we present the first report of siblings with progressive congenital aleukemic leukemia cutis, both treated successfully with myeloid leukemia chemotherapy.