Chronic myelomonocytic leukemia in childhood

A four-year-old child with recurrent infections and increasing hepatosplenomegaly over a three-year period was evaluated. Increased numbers of myeloid precursors packed the bone marrow and infiltrated the peripheral blood. A diagnosis of chronic myelogenous leukemia (CML) was considered but could not be confirmed by laboratory studies appropriate for the types of CML usually observed in childhood. Examination of the patient's peripheral blood smears revealed many atypical monocytoid cells with unipolar hairy projections. Scanning electron microscopy showed these to be leukemic monoblasts with characteristic broad-based ruffles on the cell surface. A population of myeloid precursors possessing narrow ridge-like profiles was also observed. Progressive infiltration of the spleen caused hypersplenism which necessitated splenectomy. Subsequently, massive liver and bone marrow involvement led to the patient's death. Terminally, the proliferating blast cells were demonstrated to be leukemic monoblasts by analysis of cytochemical staining patterns, surface immunoglobulins, serum lysozyme levels, and monocyte-mediated antibody-dependent cellular cytotoxicity studies. The findings in this case are most compatible with a diagnosis of chronic myelomonocytic leukemia (CMML), a condition not previously described in childhood. Several myeloproliferative disorders with prolonged survival have been reported in children, but special studies were not performed to determine which cell lines were abnormally proliferating. The similarities between these children and our patient with CMML suggest that monocyte studies may be useful in the diagnosis of these unusual disorders, provide insights into their pathogenesis, and aid in the selection of appropriate therapy.     

Tyrosine phosphorylation of proteins in primary human myeloid leukemic cells stimulated by macrophage colony-stimulating factor: Analysis by disease type and comparison with normal human hematopoietic cells

We investigated tyrosine phosphorylation of proteins in primary human leukemic cells stimulated by macrophage colony-stimulating factor (M-CSF) in 60 patients with acute myeloid leukemia (AML) and 5 patients with chronic myelomonocytic leukemia and compared the findings for leukemic cells with those of normal human monocytes and bone marrow immature hematopoietic cells. M-CSF induced tyrosine phosphorylation of p140-200, p110, p60, p44, and p42 frequently, and that of p95 and p55 less frequently, in primary myeloid leukemic cells, whereas M-CSF-induced phosphorylation of proteins was not detected in the normal human hematopoietic cells tested. Of these phosphoproteins, p140-200 was phosphorylated in all patients who responded to M-CSF and was considered to be almost identical to Fms, a product of the c-fms proto-oncogene. M-CSF-induced tyrosine phosphorylation was observed frequently (89%) in AML of French-American-British class M4 and infrequently in all other subtypes of AML, including M5. In chronic myelomonocytic leukemia, M-CSF-induced protein phosphorylation was prominent in blast crisis but was not detected in the chronic phase. Both bone marrow immature cells and mature monocytes showed low responsiveness to M-CSF. These findings for responsiveness to M-CSF were correlated with the amount of Fms in each type of cell. We also identified tyrosine phosphorylation of Vav, Shc, and extracellular signal-regulated kinase by M-CSF in some cases. These findings clarified an M-CSF-specific pattern of protein tyrosine phosphorylation and the responsiveness to M-CSF of primary human myeloid cells. Particularly, enhanced phosphorylation responses to M-CSF and increased amounts of Fms protein were observed in restricted human hematopoietic cells with a premature myelomonocytic character.     

Dendritic cells in chronic myelomonocytic leukaemia

Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.     

Isolated leukemia cutis--a case report

A 67-year-old woman with acute myelomonocytic leukemia had a clinical course characterized by the initial appearance of leukemia cutis without bone marrow involvement. When marrow involvement subsequently occurred, induction chemotherapy cleared all manifestations of the illness. Shortly thereafter, while blood and bone marrow remained in remission, the skin lesions reappeared. The introduction of 6-thioguanine, as part of the maintenance treatment protocol, resulted in the rapid and permanent disappearance of the leukemic skin infiltrates.     

A case of juvenile myelomonocytic leukemia with ocular infiltration

 We present a case of juvenile myelomonocytic leukemia (JMML) with ocular infiltration. A 1-month-old boy presented with myeloid precursors in peripheral blood and a white blood cell count  1 10×10⁹/l. His peripheral blood monocyte count was  1 1×10⁹/l, bone marrow blasts were <20%, and no Ph chromosome was identified. The boy also presented with hepatosplenomegaly, pallor, fever, and skin rash. We diagnosed this case as JMML, although hemoglobin F was within the normal range and no spontaneous colony growth was observed from peripheral blood mononuclear cells. Neither Epstein-Barr (EB) virus nor cytomegalovirus was detected by PCR in bone marrow aspirate or peripheral blood. The patient had several lesions into which JMML cells might have infiltrated, including skin, liver, spleen, oral cavity, right lung, sigmoid colon, and both eyes. To our knowledge, this is the first reported case of JMML with ocular involvement. Since infiltration of JMML cells into both eyes causes blindness, further consideration of the timing of bone marrow transplantation (BMT) in JMML is necessary. Received: February 17, 1999 / Accepted: June 21, 1999     

Combination of DNA-hypomethylating agent and hematopoietic stem cell transplantation in treatment of juvenile myelomonocytic leukemia: A case report

Introduction:Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of early childhood characterized by excessive proliferation of myelomonocytic cells and an aggressive clinical course. Allogenic hematopoietic stem cell transplantation (HSCT) is a firmly established treatment, but patients without fully matched donors have poor prognoses. Disease recurrence is the main cause of treatment failure. Meanwhile, most cases with splenomegaly present with platelet transfusion refractoriness, but splenectomy remains controversial. DNA hypermethylation correlates with poor prognosis in JMML; however, hypomethylating therapy alone does not eradicate leukemic clones. Thus, a suitable treatment with a good success rate remains elusive.Patient concerns:Here, we report our experience with a patient who suffered from recurrent fever, pallor, abdominal distention, leukocytosis, and thrombocytopenia with a silent past history and family history of somatic KRAS mutation. The patient was treated with decitabine as a bridging therapy before haploidentical HSCT. Decitabine was also used prophylactically after transplantation.Diagnosis:We arrived at a JMML diagnosis after observing leukocytosis, less than 20% blast cells in the peripheral blood and bone marrow, increased monocyte counts, negativity for the BCR-ABL fusion gene, positivity for somatic KRAS mutation, and massive splenomegaly.Interventions:The patient accepted splenectomy before HSCT, and haploidentical HSCT was applied after treatment with a DNA-hypomethylating agent. The hypomethylating agent was administered for 1 year after HSCT to prevent disease recurrence.Outcomes:The patient presented with complete remission of the disease and mild graft versus host disease for 26 months after treatment with decitabine and HSCT.Lessons:Combining haploidentical HSCT and DNA-hypomethylating agents may improve the prognosis of JMML. Meanwhile, splenectomy could be an effective option in cases with massive splenomegaly and platelet transfusion refractoriness.     

Tartrate-resistant acid phosphatase staining of monocytes in Gaucher disease

Cytochemical studies were performed on peripheral blood from 30 patients with type 1 Gaucher disease. In 29 of the patients, peripheral blood monocytes stained positively for tartrate-resistant acid phosphatase, whereas monocytes from 18 normal individuals and 14 patients with monocytosis did not. In the Gaucher patients, the percentage of monocyte positivity for tartrate-resistant acid phosphatase ranged from 2 to 97. There was no correlation between the percent monocyte staining and the degree of disease severity, as measured by hepatosplenomegaly, pancytopenia, or extent of bone disease, for the group as a whole. In Gaucher patients who had not undergone splenectomy, however, there was a significant correlation between percent monocyte staining and the degree of hepatosplenomegaly, anemia, and thrombocytopenia. The presence of tartrate-resistant acid phosphatase may be secondary to the lysosomal accumulation of glucosyl ceramide within these monocytes, although this remains to be confirmed. If so, these circulating cells may represent precursors of the Gaucher cells in tissues. Tartrate-resistant acid phosphatase staining of peripheral blood monocytes may be useful as a diagnostic marker for Gaucher type 1 disease and for further studies on the pathogenesis of the disease.     

Bulky lymphadenopathy in acute myeloid leukemia

 Two cases of acute myeloid leukemia (AML) presenting with bulky adenopathy are reported. Both patients were febrile at admission and showed massive and diffuse lymph node involvement, hepatomegaly, and splenomegaly. Erythematopapular leukemic skin lesions were present in one case at the onset and developed in the other at the time of relapse. Anemia, thrombocytopenia, and moderate leukocytosis were present in both. The presence of immature cells in peripheral blood and bone marrow allowed a rapid diagnosis of AML, FAB M1, in one patient. In the other case, owing to the paucity of immature cells in peripheral blood and bone marrow, lymph node biopsy with histology, imprint cytology, and immunocytochemistry were essential for the diagnosis (AML, FAB M2, with trilineage dysplasia and basophilic involvement). Both patients achieved complete remission (CR), followed by an early relapse 3 months later. They underwent allogeneic bone marrow transplantation (BMT) from HLA identical siblings. One patient is actually alive and in CR at 6 months after BMT; the other patient showed a leukemic regrowth after transplantation and died 4 months later. Received: December 8, 1997 / Accepted: April 29, 1998     

Two murine monoclonal antibodies to peripheral blood monocyte differentiation antigens discriminate within M5 acute non-lymphoid leukemia (ANLL) cells

Two murine monoclonal antibodies (MoAbs), LAM3 and LAM7 of the IgG₁ isotype, which were produced by immunization with normal peripheral blood monocytes (PBM), were assayed in their specificity by indirect immunofluorescence against a panel of normal as well as leukemic cells. Both LAM3 and LAM7 were reactive with PBM while LAM3 also recognized platelets. Neither MoAb showed reactivity with erythrocytes, granulocytes, or resting and mitogen activated B and T lymphocytes. The reactivity with bone marrow cells correlated with the degree of monocyte contamination. Among the 62 cases of leukemia tested, which included three cases of B-CLL, 19 cases of ALL, and 40 cases of ANLL, both MoAbs reacted highly homogenously only with M5b ANLL cells. These findings indicate that the two MoAbs, which recognize two distinct epitopes, represent useful markers in the differential diagnosis of M5b ANLL.     

Analysis of antigenic determinants on human monocytes and macrophages

Mo1, 2, 3, and 4, and Plt-1 are a series of five distinct antigens detected on the surface of human peripheral blood monocytes by mouse monoclonal antibodies. Mo2 and 3 are restricted to the monocyte- macrophage series, while Mo1, as previously reported, is also expressed by human granulocytes and null cells. Mo3, as distinguished from Mo1 and Mo2, is weakly expressed by virgin peripheral blood monocytes but becomes well expressed if monocytes are cultured overnight at 37 degrees C. Mo4 is coexpressed by monocytes and platelets, while Plt-1 appears to be a platelet-specific antigen whose detection on monocytes reflects adherence of platelets to monocyte membranes. That Mo2-4 are true monocyte antigens is demonstrated by their resynthesis following protease treatment of monocytes (Mol expression is resistant to proteolytic digestion). During myeloid-monocyte differentiation, the Mo antigens are infrequently expressed by immature myeloid cells but are found at higher frequency on leukemic monocytic forms. Macrophages from cultured peripheral blood monocytes and HL-60 cells exposed to lymphokines or phorbol diester express Mo1-4, but noncirculating peritoneal macrophages lack Mo3. The Mo antigens are differentiation markers whose expression reflects membrane heterogeneity during myeloid- monocyte-macrophage maturation.     

Incorporating flow cytometry and next-generation sequencing in the diagnosis of CMML. Are we ready for prime?

In the last version of the WHO classification of myeloid malignancies, flow cytometry and molecular investigation are listed as potentially useful, yet non-essential diagnostic tools in hard-to-recognize chronic myelomonocytic leukemias (CMML). Flow recognition of CMML was initially based on an increase in the fraction of peripheral blood, CD14⁺,CD16^- classical monocytes ≥94% of total monocytes. An associated inflammatory disease can preclude the detection of classical monocyte fraction increase by inducing accumulation of CD14⁺,CD16⁺ intermediate monocytes. In such a situation, decrease in the Slan⁺,CD14^low,CD16⁺ non-classical monocyte fraction below 1.7% still supports CMML diagnosis. This robust, two-step flow cytometry assay identifies CMML with a very high sensitivity. Otherwise, detection of one or several acquired gene mutations with high variant allele frequency supports the diagnosis of CMML, oligomonocytic CMML or clonal monocytosis of clinical significance. Together, recent investigations support integration of flow cytometry analysis of peripheral blood monocyte subsets and new generation sequencing of a panel of 20–30 recurrently mutated genes in the diagnostic work-up of CMML.     

How do normal and leukemic white blood cells egress from the bone marrow?

Summary Under normal circumstances only mature granulocytes and monocytes cross the bone marrow sinus wall, a trilaminar structure consisting of endothelial cells, a discontinuous basal membrane and an adventitial cell layer in order to get access to the blood circulation. In leukemia, however, immature white blood cells are able to traverse the barrier and to appear in the blood stream. Very little is known about the regulatory processes which govern the egress of white blood cells in healthy individuals and their malignant counterparts in patients with leukemia. The results of the few studies performed to address this question in animal and human leukemias all agree that the extent to which adventitial cells (fibroblasts) cover the endothelium in bone marrow is drastically reduced. This implies altered interactions between the leukemic and adventitial cells and their extracellular matrix. We propose here a model to explain the egress of normal cells and their leukemic counterparts. It is based upon our own experimental data and the general at present limited knowledge of the subject. It is hoped that this model will stimulate further research into this important aspect of leukemogenesis.     

Receptor for platelet-activating factor (PAF) is not detectable by flow cytometry on the surface of myeloid leukemic cells

Flow cytometry was applied to test for platelet-activating-factor receptor (PAF-R) presence on the membranes of acute myeloid leukemia (AML) cells. We have used six human AML cell lines and freshly taken density gradient separated blasts from the bone marrow of ten AML patients covering the majority of French–American–British (FAB) subtypes. Additionally, we have used one histiocytic lymphoma cell line and mature human granulocytes/monocytes as controls. Our results indicate lack of membrane PAF-R on AML of all FAB subtypes tested. This was particularly true for the more mature and differentiated subtypes M₄ and M₅, including monocytic cell elements, and the promyelocytic M₃ AML. In contrast, membrane PAF-R could be easily detected in a histiocytic lymphoma cell line and mature granulocytes/monocytes from peripheral blood used as positive controls. In conclusion, this observation precludes the use of membrane PAF-R as an immunophenotypic marker for AML classification or detection of minimal residual disease.     

Concordance among hematopathologists in classifying blasts plus promonocytes: A bone marrow pathology group study

Enumeration of blasts and promonocytes is essential for World Health Organization (WHO) classification of myelomonocytic neoplasms. The accuracy of distinguishing blasts, promonocytes and monocytes, including normal vs abnormal monocytes, remains controversial. The objective of this analysis is to assess concordances between experienced hematopathologists in classifying cells as blasts, promonocytes, and monocytes according to WHO criteria. Each of 11 hematopathologists assessed glass slides from 20 patients [12 with chronic myelomonocytic leukemia (CMML) and 8 with acute myeloid leukemia (AML)] including blood and BM aspirate smears, and limited nonspecific esterase (NSE) stains. All cases were blindly reviewed. Fleiss’ extension of Cohen's kappa for multiple raters was used on these variables, separately for peripheral blood (PB) and bone marrow (BM). Spearman's rank correlation was used to assess correlations between each pair of hematopathologists for each measurement. For the classification based on the sum of blasts and promonocytes in the BM, Fleiss’ kappa was estimated as 0.744. For PB, categorizing patients according to the sum of blasts and promonocytes, Fleiss’ kappa was estimated as 0.949. Distinction of abnormal monocytes from normal monocytes in PB did not achieve a good concordance and showed strong evidence of differences between hematopathologists (P < .0001). The hematopathologists achieved a good concordance rate of 74% in CMML vs AML classification and a high k rate, confirming that criteria for defining the blasts equivalents (blasts plus promonocytes) could be applied consistently. Identification of monocyte subtypes (abnormal vs normal) was not concordant. Our results support the practice of combining blasts/promonocytes into a single category.     

Evidence for a lymphotropic nature of circulating plasmacytoid monocytes: findings from a case of CD56+ chronic myelomonocytic leukemia

Abstract: Because the cells previously designated plasmacytoid T cells share major immunophenotypic features with cells of the mononuclear-phagocyte system, they have been re-named and are now known as plasmacytoid monocytes (PM). We describe a unique case of chronic myelomonocytic leukemia with circulating PM. The patient, a 48-year-old man, presented initially with refractory anemia. Four years later his general condition deteriorated, accompanied by an increase in leukocytes to 200 000/μl blood. The bone marrow histology was interpreted as compatible with a diagnosis of chronic myelomonocytic leukemia. Two months before he died, the patient developed generalized lymphadenopathy clinically simulating malignant lymphoma. Histologic examination of an axillary lymph node revealed diffuse infiltration by PM. The PM in the lymph node and some circulating cells closely resembling PM expressed L-selectin, a finding that could be interpreted as a morphologic correlate of their marked lymphotropism. The detection of large numbers of CD56/CD33 double-positive circulating blast cells by FACS analysis strongly supported the diagnosis of a leukemia of myelogenous origin. The patient died of tumor cachexia. Autopsy revealed widespread leukemic infiltrates (always containing clusters of PM) in bone marrow, spleen, liver, lymph nodes, and mucosa-associated lymphoid tissue of the oropharynx. The final diagnosis was one of chronic myelomonocytic leukemia with marked lymphotropism and partial differentiation towards PM. We consider that the rare instances of a hematologic tumor with differentiation towards PM should be classified amongst the myelogenous leukemias.     

Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined.     

Expression of two natural killer cell antigens, H-25 and H-366, by human immature myeloid cells and by erythroid and granulocytic/monocytic colony-forming units

Two monoclonal antibodies (MoAbs), H-25 and H-366, shown previously to react with human peripheral blood large granular lymphocytes with natural killer (NK) cell activity and some peripheral blood monocytes, have now been shown to also react with a significant proportion of the myeloid and erythroid precursor cells in human bone marrow and peripheral blood. In FACS IV cell sorting and immune rosetting of bone marrow cells, the antigens recognized by H-25 and H-366 were found to be expressed on most blasts and promyelocytes but sequentially fewer of the more mature cells of the myeloid lineage. Both antigens were also found on most monocytes but only a minor proportion of lymphoid and nucleated red cells in the bone marrow. In vitro assays detecting hematopoietic colony-forming units revealed that these antigens are expressed by virtually all mature erythroid colony-forming units (day-7 CFU-E), and the majority of the more primitive erythroid burst forming units (day-14 BFU-E). H-25 but not H-366 was also found on a variable proportion of the day-7 and day-14 granulocytic/monocytic colony- forming units (CFU-GM) in the bone marrow. The same type of precursor cells are also found in the H-25 and H-366 positive cell populations isolated from peripheral blood. In preliminary testing of cells from acute leukemic patients, FACS analysis showed that both antigens are also expressed on leukemic cells from patients with T cell acute lymphocytic leukemia and with myeloid leukemias. These studies demonstrate that the H-25 and H-366 positive NK cells in the peripheral blood retain some of the cell surface properties of early hematopoietic precursor cells, thus providing further evidence supporting the bone marrow origin of NK cells.     

Theileria annulata sporozoite targets

Bovine peripheral blood mononuclear cells (PBM) infected in vitro with Theileria annulata sporozoites have previously been characterized as MHC class II⁺ mature macrophages. The ability of T. annulata sporozoites to infect different subpopulations of MHC class II⁺ bovine monocytes was investigated. Cells were labelled with monocyte specific monoclonal antibodies (MoAb) and isolated using magnetic cell sorting (MACS). Sporozoites infected both immature and mature monocytes, but more readily infected the mature population. A potential ligand for sporozoite entry is the elastin receptor which is expressed mainly on the immature population of monocytes and not on B cells or T cells. T. annulata sporozoites infected elastin receptor positive and negative cell populations equally well. Infected immature cells lost the expresstion of elastin receptors and the immature marker, subsequently expressing the mature marker. All monocytes lost the expression of CD14 (the LPS receptor) upon infection with sporozoites. The infection of specific populations and subsequent alterations in phenotype may alter the function of these cells and play an important role in disease pathogenesis.     

Hematopoietic progenitor cell colony growth differentiates chronic myelomonocytic leukemia from reactive monocytosis

In the absence of a cytogenetic abnormality or overt dysplasia, chronic myelomonocytic leukemia (CMML) may be difficult to be distinguished from reactive monocytosis. We have previously described a typical growth pattern in CMML patients, i.e., 'pseudonormal' colonies resembling granulocytic colonies but consisting entirely of monocytic cells when stained. To study the utility of the colony forming unit cell assay (CFU-C) as a diagnostic tool in patients with monocytosis, we analyzed a cohort of 48 consecutive patients referred to our institution with peripheral blood monocytosis. Thirty-six patients fulfilled the WHO criteria for CMML; 12 were diagnosed with reactive monocytosis. Of the patients with CMML, 28 showed pseudonormal growth with or without leukemic cluster growth, another four showed exclusively leukemic growth. None of the patients with reactive monocytosis showed either leukemic or pseudonormal growth. With a specificity of 100% and a sensitivity of 89%, the CFU-C assay has a unique potential to distinguish CMML from reactive monocytosis.     

Elevated low density lipoprotein receptor activity in leukemic cells with monocytic differentiation

The receptor-mediated degradation of 125I-low density lipoprotein (LDL) was compared in normal white blood cells and leukemic cells. The cells were isolated from the peripheral blood and bone marrow of healthy subjects and patients with newly diagnosed leukemia. The cells from most of the 40 consecutive patients with acute myelogenous leukemia showed markedly higher degradation rates as compared to mononuclear cells and granulocytes from peripheral blood and nucleated cells from the bone marrow of healthy individuals. Leukemic cells from patients with monocytic (FAB-M5) or myelomonocytic leukemia (FAB-M4) exhibited the highest degradation rates. The rate of receptor-mediated degradation of 125I-LDL was also high in leukemic cells from all three patients with chronic myelogenous leukemia in blast crisis, as well as in two of three patients with acute undifferentiated leukemia. In contrast, leukemic cells isolated from two patients with acute lymphoblastic leukemia showed low rates. In most cases, there was little difference in LDL receptor activity between leukemic cells isolated from peripheral blood and those from bone marrow. Hypocholesterolemia was a frequent finding in the leukemic patients. There was an inverse correlation between the plasma cholesterol level and the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. Studies are now in progress to investigate the possibilities of using LDL as a carrier of cytotoxic drugs in the treatment of leukemia.