Diagnostic Significance of Detecting Dysgranulopoiesis in Chronic Myeloid Leukemia

Yin Xu, MD, PhD, Michelle M. Dolan, MD, Phuong L. Nguyen, MD

Disclosures

Am J Clin Pathol. 2003;120(5) 

In This Article

Abstract and Introduction

We examined whether the detection of dysgranulopoiesis in blood or bone marrow would predict chronic myeloid leukemia (CML) in transformation in 31 cases that fulfilled World Health Organization criteria for disease transformation, including 14 in accelerated phase (AP), 10 in myeloid blast crisis (MBC), and 7 in lymphoid blast crisis (LBC). Dysgranulopoiesis was detected in 7 cases, 6 in AP and 1 in MBC, but not in LBC or chronic phase cases. In 3 AP cases, dysgranulopoiesis was identified 2 to 5 months before the morphologic diagnosis of transformation. Two AP cases showed no dysgranulopoiesis in previous blood or marrow smears. For 2 cases (1 AP and 1 MBC), no previous blood or marrow specimens were available. Cytogenetic information was available for 6 of 7 cases with and 22 of 24 cases without dysgranulopoiesis. All cases with dysgranulopoiesis had secondary chromosome abnormalities in addition to t(9;22). In 5 (83%) of 6 cases with dysgranulopoiesis, the secondary chromosome abnormalities included abnormalities of 17p. In contrast, none of the 22 cases of CML in AP or BC but without dysgranulopoiesis showed 17p abnormalities (P = .001). Our findings demonstrated that dysgranulopoiesis was associated strongly with chromosome 17p abnormalities and may indicate the onset of or impending disease transformation.

Chronic myeloid leukemia (CML) is a clonal disorder of hematopoietic stem cells that accounts for 15% to 20% of all leukemias in adults. The disease is characterized by bcr-abl gene fusion typically resulting from t(9;22)(q34;q11.2).[1] The product of the translocation is a constitutively active bcr-abl tyrosine kinase[2,3] that is believed to be the causative leukemogenic agent.[4,5] CML usually progresses through 3 clinical stages: an indolent chronic phase lasting for 3 to 5 years followed by an accelerated phase (AP) and, ultimately, blast crisis (BC), a terminal, acute leukemic phase; the disease also can transform into BC without a detectable AP. Such clinical transformation of CML to AP or BC has been demonstrated to be associated with additional genetic changes.

The progressive clinical deterioration that occurs in patients with CML is accompanied by a number of morphologic changes in the blood and bone marrow. While dysgranulopoiesis is not a characteristic feature of the chronic phase of CML, it occasionally is observed in transformed CML.[6] Dysgranulopoiesis originally was described in myelodysplastic syndrome (MDS) and in some cases of primary and secondary acute myeloid leukemia (AML).[7,8,9] In MDS and AML, dysgranulopoiesis with pseudo-Pelger-Hüet anomaly has been reported to be associated with loss of chromosome 17p.[10,11,12] Among recurring chromosomal abnormalities in CML in evolution, chromosome 17p anomalies are the third most common secondary abnormality following trisomy 8 and gain of an extra Philadelphia chromosome.[13] An association between chromosome 17p abnormalities and dysgranulopoiesis in BC has been reported in a single study[14]; to our knowledge, this association has not been confirmed by other studies. The purpose of the present study was to determine the frequency of dysgranulopoiesis in CML, its specificity with respect to disease progression and chromosome 17p abnormalities, and whether detecting dysgranulopoiesis in blood or bone marrow is of value in predicting CML transformation.

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