1. Lymphoid Preponderance and the Absence of Basophilia
and Splenomegaly Are the Characteristics of Minor-bcr
Positive Chronic Myelogenous Leukemia
Mina Hur1,2, Eun Young Song1, Sung-Ha Kang2, Dong-Hoon Shin2,
Ji Yeon Kim1, Sung Sup Park1, and Han Ik Cho1
1Department of Clinical Pathology, Seoul National University College of Medicine, Seoul, Korea;
2Department of Clinical Pathology, Hallym University College of Medicine, Seoul, Korea;
INTRODUCTION
Chronic myelogenous leukemia (CML) with a minor bcr-abl transcript is a rare entity with only 16 cases available in the literature. Among them, three cases presented with an onset of blast crisis (BC), and the others were in chronic or accelerating phase at diagnosis.
The biological significance of m-bcr CML remains still unclear. While some authors suggested that the cases with this molecular hallmark resulted in more aggressive diseases, not all of the reported cases had aggressive outcomes.
We here describe another case of m-bcr CML, which showed the morphological features resembling CMML and an indolent clinical course, and review the previous literatures.
CASE REPORT
A 66-year-old female was admitted in August 1998 with a high white blood cell (WBC) count of 34.6109/L, which was detected on a routine yearly physical checkup. She had no palpable spleen, liver or lymph node.
WBC differential was: 1% myeloblasts, 2% promyelocytes, 7% myelocytes, 3% metamyelocytes, 58% band forms and segmented neutrophils, 4% eosinophils, 16% lymphocytes, and 9% monocytes. The hemoglobin level was 15.0 g/dL and the platelet count was 223109/L.
Examination of bone marrow specimen revealed hypercellularity of 90% with granulocytic and mild megakaryocytic hyperplasia, and estimated M:E ratio was 4.5:1. Differential count showed 2.7% blasts, 7.8% eosinophils, and 0.8% basophils. Neutrophil alkaline phophatase (NAP) score was 8.
Cytogenetic study showed a standard Ph translocation in all of 20 metaphase cells: 46,XX,t(9;22)(q34;q11).
RT-PCR demonstrated a minor bcr-abl transcript (e1a2 type) without a major b3a2 or b2a2 fusion transcript.
She was diagnosed as CML in chronic phase, and hydroxyurea treatment was started. Her clinical course has been indolent with no remarkable change on her hematological features over the period of nearly three years.
DISCUSSION
The most striking feature of m-bcr CML was known to be monocytosis resembling chronic myelomonocytic leukemia. Review of the 17 cases of m-bcr CML including this case showed the presence of monocytosis and the absence of basophilia and splenomegaly in 46.7%, 73.3%, and 66.7% of patients, respectively. In addition, all of the three cases with an onset of BC didn’t show monocytosis at diagnosis. These imply that monocytosis is not a prerequisite to determine the hematological phenotype of m-bcr CML, and is confined to some patients in chronic phase, though it might be one of the peculiar hematological features.
Although the hematological features or clinical outcomes were variable in m-bcr CML cases, all of the three cases with an onset of BC showed the lymphoid crisis implying an increased lymphoid leukemogenicity of minor bcr-abl transcripts. A case with an evolution to the lymphoid BC was also reported by Nakamural et al. This finding might be suggestive of the lymphoid preponderance of m-bcr CML, although there was a report of progression to the hybrid type BC.
CONCLUSION
Conclusively, monocytosis, which is confined to the chronic phase, is not a conspicuous feature of m-bcr CML patients, and the absence of basophilia and splenomegaly is a more frequent finding than monocytosis alone.
Although the clinical courses are variable, lymphoid preponderance is a characteristic finding in blastic phase of m-bcr CML.