Juvenile myelomonocytic leukemia (JMML) with the hematologic phenotype of severe β thalassemia

Abstract

A 3-year-old Filipino-American child with recurrent fever, splenomegaly, anemia, and thrombocytopenia, was found to have a hemoglobin F level of 76.9%. His reticulocyte count was elevated (4.3%), and erythroblasts were present in his peripheral blood. The child's erythrocytes were microcytic (MCV 66.9 fl) but his serum ferritin level was normal. His bone marrow at initial presentation demonstrated normal cellularity without an increase in blast cells. The disease progressed with worsening anemia, leukocytosis, and thrombocytopenia, with increased blasts in his marrow and the appearance of a medi-astinal mass. His liver, spleen, and lymph nodes were found to be infiltrated with myelo-blasts, supporting a diagnosis of juvenile myelomonocytic leukemia (JMML). Analysis of the child's Hb F showed a G / A ratio of 2.2, which was within the characteristic range for JMML. A globin synthesis study using blood reticulocytes showed an /non-globin synthesis ratio of 2.24, typical of severe homozygous thalassemia. Southern blot analysis of blood-leukocyte DNA from the patient and his parents demonstrated no apparent abnormality in the-globin gene promoter or coding regions. The elevated level of Hb F in this child with JMML appeared to be part of an acquired Cooley's anemia-like hema-tologic phenotype. Am. J. Hematol. 58:67-71, 1998.

Recurrent Fever in Children

“…In the differential diagnosis of recurrent fever, neoplasms should be ruled out, even if they are usually associated with prolonged fever [ 108 ]; only lymphoma, juvenile myelomonocytic leukemia and atrial myxoma have been reported to cause recurrent fever in children [ 109 , 110 , 111 , 112 , 113 , 114 ]. Leukemia and lymphoma are the two most common neoplasms that could present with recurrent fever.…”

Recurrent fever in children

“…In the differential diagnosis of recurrent fever, neoplasms should be ruled out, even if they are usually associated with prolonged fever [108]; only lymphoma, juvenile myelomonocytic leukemia and atrial myxoma have been reported to cause recurrent fever in children [109][110][111][112][113][114]. Leukemia and lymphoma are the two most common neoplasms that could present with recurrent fever.…”

Classical meets malignant hematology: a case of acquired εγδβ-thalassemia in clonal hematopoiesis

“…Acquired alpha-thalassemias are associated mainly with myelodysplastic neoplasms (MDS) and are caused either by somatic deletions of the alpha-globin gene cluster on chromosome 16p13.3 limited to the hematological clone or, more commonly, by inactivating somatic variants of the trans-acting regulatory factor, ATRX, leading to downregulation of alpha-globin gene expression 3 . In contrast, acquired somatic genetic variants causing reduced beta-globin production and leading to a beta-thalassemic phenotype are a rarity, and only a few, single cases have been described so far [4][5][6][7] .…”

“…In contrast to acquired forms of alpha-thalassemia that are an established observation in MDS, acquired beta-thalassemia are extremely rare and described in only a few cases. So far, acquired (γδ)β-thalassemias have been described in MDS 4,5,7 , acute myeloid leukemia 8 , juvenile myelomonocytic leukemia 6 and common variable immunodeficiency 9 . In the present patient, bone marrow investigations would be necessary to differentiate between clonal cytopenia of unknown significance (CCUS) and a hematologic neoplasm, such as MDS, as final diagnosis.…”

“…Interestingly, none of the previously described cases of acquired betathalassemia exhibited an HbA2 increase suggesting the presence of deleterious aberrations of both the beta-and delta-globin genes. However, most of those patients presented with an increase in HbF pointing to intact gamma-globin genes [5][6][7][8] . Thus, these cases most likely represent delta-beta-thalassemias caused by deletions in the beta-globin gene cluster affecting the delta-and beta-globin gene, but leaving the gamma-globin genes intact.…”